Cellular Plasticity: A Route to Senescence Exit and Tumorigenesis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Overcoming Senescence via Escape Instigates Neoplasticity and Genomic Instability in Pre-Tumoral Cells
3. Overcoming Senescence via Bypass Preserves a Stable Tumor Genome
4. A Dualistic Model for Tumor Initiation
5. SASP: A Major Determinant of Tumorigenesis
6. Acquisition of Plasticity Allows Immunoevasion by Senescent Cells
7. Senescence Escape Is a Driver of Tumor Resilience
8. Cellular Plasticity Can Result from an Interplay between Senescent Cells and the Immune Component
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Muñoz-Espín, D.; Serrano, M. Cellular Senescence: From Physiology to Pathology. Nat. Rev. Mol. Cell Biol. 2014, 15, 482–496. [Google Scholar] [CrossRef]
- Salama, R.; Sadaie, M.; Hoare, M.; Narita, M. Cellular Senescence and Its Effector Programs. Genes Dev. 2014, 28, 99–114. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hernandez-Segura, A.; Nehme, J.; Demaria, M. Hallmarks of Cellular Senescence. Trends Cell Biol. 2017, 28, 436–453. [Google Scholar] [CrossRef] [PubMed]
- Abbadie, C.; Pluquet, O.; Pourtier, A. Epithelial Cell Senescence: An Adaptive Response to Pre-Carcinogenic Stresses? Cell. Mol. Life Sci. 2017, 74, 4471–4509. [Google Scholar] [CrossRef]
- Demaria, M.; Ohtani, N.; Youssef, S.A.; Rodier, F.; Toussaint, W.; Mitchell, J.R.; Laberge, R.-M.; Vijg, J.; Van Steeg, H.; Dollé, M.E.T.; et al. An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA. Dev. Cell 2014, 31, 722–733. [Google Scholar] [CrossRef] [Green Version]
- Ritschka, B.; Storer, M.; Mas, A.; Heinzmann, F.; Ortells, M.C.; Morton, J.P.; Sansom, O.J.; Zender, L.; Keyes, W.M. The Senescence-Associated Secretory Phenotype Induces Cellular Plasticity and Tissue Regeneration. Genes Dev. 2017, 31, 172–183. [Google Scholar] [CrossRef] [Green Version]
- Hiebert, P.; Wietecha, M.S.; Cangkrama, M.; Haertel, E.; Mavrogonatou, E.; Stumpe, M.; Steenbock, H.; Grossi, S.; Beer, H.-D.; Angel, P.; et al. Nrf2-Mediated Fibroblast Reprogramming Drives Cellular Senescence by Targeting the Matrisome. Dev. Cell 2018, 46, 145–161.e10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Da Silva-Álvarez, S.; Guerra-Varela, J.; Sobrido-Cameán, D.; Quelle, A.; Barreiro-Iglesias, A.; Sánchez, L.; Collado, M. Cell Senescence Contributes to Tissue Regeneration in Zebrafish. Aging Cell 2020, 19, e13052. [Google Scholar] [CrossRef]
- Hinz, B. The Role of Myofibroblasts in Wound Healing. Curr. Res. Transl. Med. 2016, 64, 171–177. [Google Scholar] [CrossRef]
- Desmoulière, A.; Redard, M.; Darby, I.; Gabbiani, G. Apoptosis Mediates the Decrease in Cellularity during the Transition between Granulation Tissue and Scar. Am. J. Pathol. 1995, 146, 56–66. [Google Scholar]
- Jeon, O.H.; Kim, C.; Laberge, R.-M.; Demaria, M.; Rathod, S.; Vasserot, A.P.; Chung, J.W.; Kim, D.H.; Poon, Y.; David, N.; et al. Local Clearance of Senescent Cells Attenuates the Development of Post-Traumatic Osteoarthritis and Creates a pro-Regenerative Environment. Nat. Med. 2017, 23, 775–781. [Google Scholar] [CrossRef]
- Schafer, M.J.; White, T.A.; Iijima, K.; Haak, A.J.; Ligresti, G.; Atkinson, E.J.; Oberg, A.L.; Birch, J.; Salmonowicz, H.; Zhu, Y.; et al. Cellular Senescence Mediates Fibrotic Pulmonary Disease. Nat. Commun. 2017, 8, 14532. [Google Scholar] [CrossRef]
- Wiley, C.D.; Brumwell, A.N.; Davis, S.S.; Jackson, J.R.; Valdovinos, A.; Calhoun, C.; Alimirah, F.; Castellanos, C.A.; Ruan, R.; Wei, Y.; et al. Secretion of Leukotrienes by Senescent Lung Fibroblasts Promotes Pulmonary Fibrosis. JCI Insight 2019, 4, e130056. [Google Scholar] [CrossRef] [Green Version]
- Krtolica, A.; Parrinello, S.; Lockett, S.; Desprez, P.Y.; Campisi, J. Senescent Fibroblasts Promote Epithelial Cell Growth and Tumorigenesis: A Link between Cancer and Aging. Proc. Natl. Acad. Sci. USA 2001, 98, 12072–12077. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cirri, P.; Chiarugi, P. Cancer Associated Fibroblasts: The Dark Side of the Coin. Am. J. Cancer Res. 2011, 1, 482–497. [Google Scholar] [PubMed]
- Burd, C.E.; Sorrentino, J.A.; Clark, K.S.; Darr, D.B.; Krishnamurthy, J.; Deal, A.M.; Bardeesy, N.; Castrillon, D.H.; Beach, D.H.; Sharpless, N.E. Monitoring Tumorigenesis and Senescence in Vivo with a P16INK4a-Luciferase Model. Cell 2013, 152, 340–351. [Google Scholar] [CrossRef] [Green Version]
- Dvorak, H.F. Tumors: Wounds That Do Not Heal. Similarities between Tumor Stroma Generation and Wound Healing. N. Engl. J. Med. 1986, 315, 1650–1659. [Google Scholar] [CrossRef]
- MacCarthy-Morrogh, L.; Martin, P. The Hallmarks of Cancer Are Also the Hallmarks of Wound Healing. Sci. Signal. 2020, 13, 648. [Google Scholar] [CrossRef]
- O’Byrne, K.J.; Dalgleish, A.G. Chronic Immune Activation and Inflammation as the Cause of Malignancy. Br. J. Cancer 2001, 85, 473–483. [Google Scholar] [CrossRef] [PubMed]
- Nieto, M.A.; Huang, R.Y.-J.; Jackson, R.A.; Thiery, J.P. EMT: 2016. Cell 2016, 166, 21–45. [Google Scholar] [CrossRef] [Green Version]
- Schiebinger, G.; Shu, J.; Tabaka, M.; Cleary, B.; Subramanian, V.; Solomon, A.; Gould, J.; Liu, S.; Lin, S.; Berube, P.; et al. Optimal-Transport Analysis of Single-Cell Gene Expression Identifies Developmental Trajectories in Reprogramming. Cell 2019, 176, 928–943.e22. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Grosse-Wilde, A.; D’Hérouël, A.F.; McIntosh, E.; Ertaylan, G.; Skupin, A.; Kuestner, R.E.; Del Sol, A.; Walters, K.A.; Huang, S. Stemness of the Hybrid Epithelial/Mesenchymal State in Breast Cancer and Its Association with Poor Survival. PLoS ONE 2015, 10, e0126522. [Google Scholar] [CrossRef]
- Grande, M.T.; Sánchez-Laorden, B.; López-Blau, C.; De Frutos, C.A.; Boutet, A.; Arévalo, M.; Rowe, R.G.; Weiss, S.J.; López-Novoa, J.M.; Nieto, M.A. Snail1-Induced Partial Epithelial-to-Mesenchymal Transition Drives Renal Fibrosis in Mice and Can Be Targeted to Reverse Established Disease. Nat. Med. 2015, 21, 989–997. [Google Scholar] [CrossRef] [Green Version]
- Lovisa, S.; LeBleu, V.S.; Tampe, B.; Sugimoto, H.; Vadnagara, K.; Carstens, J.L.; Wu, C.-C.; Hagos, Y.; Burckhardt, B.C.; Pentcheva-Hoang, T.; et al. Epithelial-to-Mesenchymal Transition Induces Cell Cycle Arrest and Parenchymal Damage in Renal Fibrosis. Nat. Med. 2015, 21, 998–1009. [Google Scholar] [CrossRef]
- Adams, T.S.; Schupp, J.C.; Poli, S.; Ayaub, E.A.; Neumark, N.; Ahangari, F.; Chu, S.G.; Raby, B.A.; DeIuliis, G.; Januszyk, M.; et al. Single-Cell RNA-Seq Reveals Ectopic and Aberrant Lung-Resident Cell Populations in Idiopathic Pulmonary Fibrosis. Sci. Adv. 2020, 6, eaba1983. [Google Scholar] [CrossRef]
- Choi, J.; Park, J.-E.; Tsagkogeorga, G.; Yanagita, M.; Koo, B.-K.; Han, N.; Lee, J.-H. Inflammatory Signals Induce AT2 Cell-Derived Damage-Associated Transient Progenitors That Mediate Alveolar Regeneration. Cell Stem Cell 2020, 27, 366–382.e7. [Google Scholar] [CrossRef]
- Habermann, A.C.; Gutierrez, A.J.; Bui, L.T.; Yahn, S.L.; Winters, N.I.; Calvi, C.L.; Peter, L.; Chung, M.-I.; Taylor, C.J.; Jetter, C.; et al. Single-Cell RNA Sequencing Reveals Profibrotic Roles of Distinct Epithelial and Mesenchymal Lineages in Pulmonary Fibrosis. Sci. Adv. 2020, 6, eaba1972. [Google Scholar] [CrossRef]
- Kobayashi, Y.; Tata, A.; Konkimalla, A.; Katsura, H.; Lee, R.F.; Ou, J.; Banovich, N.E.; Kropski, J.A.; Tata, P.R. Persistence of a Regeneration-Associated, Transitional Alveolar Epithelial Cell State in Pulmonary Fibrosis. Nat. Cell Biol. 2020, 22, 934–946. [Google Scholar] [CrossRef]
- Strunz, M.; Simon, L.M.; Ansari, M.; Kathiriya, J.J.; Angelidis, I.; Mayr, C.H.; Tsidiridis, G.; Lange, M.; Mattner, L.F.; Yee, M.; et al. Alveolar Regeneration through a Krt8+ Transitional Stem Cell State That Persists in Human Lung Fibrosis. Nat. Commun. 2020, 11, 3559. [Google Scholar] [CrossRef] [PubMed]
- Ocampo, A.; Reddy, P.; Martinez-Redondo, P.; Platero-Luengo, A.; Hatanaka, F.; Hishida, T.; Li, M.; Lam, D.; Kurita, M.; Beyret, E.; et al. In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. Cell 2016, 167, 1719–1733.e12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Doeser, M.C.; Schöler, H.R.; Wu, G. Reduction of Fibrosis and Scar Formation by Partial Reprogramming In Vivo. Stem Cells 2018, 36, 1216–1225. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- de Lázaro, I.; Yilmazer, A.; Nam, Y.; Qubisi, S.; Razak, F.M.A.; Degens, H.; Cossu, G.; Kostarelos, K. Non-Viral, Tumor-Free Induction of Transient Cell Reprogramming in Mouse Skeletal Muscle to Enhance Tissue Regeneration. Mol. Ther. 2019, 27, 59–75. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mosteiro, L.; Pantoja, C.; Alcazar, N.; Marión, R.M.; Chondronasiou, D.; Rovira, M.; Fernandez-Marcos, P.J.; Muñoz-Martin, M.; Blanco-Aparicio, C.; Pastor, J.; et al. Tissue Damage and Senescence Provide Critical Signals for Cellular Reprogramming in Vivo. Science 2016, 354, aaf4445. [Google Scholar] [CrossRef]
- Ansieau, S.; Bastid, J.; Doreau, A.; Morel, A.-P.P.; Bouchet, B.P.; Thomas, C.; Fauvet, F.; Puisieux, I.; Doglioni, C.; Piccinin, S.; et al. Induction of EMT by Twist Proteins as a Collateral Effect of Tumor-Promoting Inactivation of Premature Senescence. Cancer Cell 2008, 14, 79–89. [Google Scholar] [CrossRef] [Green Version]
- Morel, A.-P.; Hinkal, G.W.; Thomas, C.; Fauvet, F.; Courtois-Cox, S.; Wierinckx, A.; Devouassoux-Shisheboran, M.; Treilleux, I.; Tissier, A.; Gras, B.; et al. EMT Inducers Catalyze Malignant Transformation of Mammary Epithelial Cells and Drive Tumorigenesis towards Claudin-Low Tumors in Transgenic Mice. PLoS Genet. 2012, 8, e1002723. [Google Scholar] [CrossRef] [Green Version]
- Collado, M.; Blasco, M.A.; Serrano, M. Cellular Senescence in Cancer and Aging. Cell 2007, 130, 223–233. [Google Scholar] [CrossRef] [Green Version]
- Hanahan, D.; Weinberg, R.A. Hallmarks of Cancer: The Next Generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [Green Version]
- Childs, B.G.; Gluscevic, M.; Baker, D.J.; Laberge, R.-M.; Marquess, D.; Dananberg, J.; van Deursen, J.M. Senescent Cells: An Emerging Target for Diseases of Ageing. Nat. Rev. Drug Discov. 2017, 16, 718–735. [Google Scholar] [CrossRef] [Green Version]
- Maciejowski, J.; de Lange, T. Telomeres in Cancer: Tumour Suppression and Genome Instability. Nat. Rev. Mol. Cell Biol. 2017, 18, 175–186. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Faget, D.V.; Ren, Q.; Stewart, S.A. Unmasking Senescence: Context-Dependent Effects of SASP in Cancer. Nat. Rev. Cancer 2019, 19, 439–453. [Google Scholar] [CrossRef] [PubMed]
- Puisieux, A.; Pommier, R.M.; Morel, A.P.; Lavial, F. Cellular Pliancy and the Multistep Process of Tumorigenesis. Cancer Cell 2018, 33, 164–172. [Google Scholar] [CrossRef] [Green Version]
- Puisieux, A.; Brabletz, T.; Caramel, J. Oncogenic Roles of EMT-Inducing Transcription Factors. Nat. Cell Biol. 2014, 16, 488–494. [Google Scholar] [CrossRef] [PubMed]
- Braig, M.; Lee, S.; Loddenkemper, C.; Rudolph, C.; Peters, A.H.F.M.; Schlegelberger, B.; Stein, H.; Dörken, B.; Jenuwein, T.; Schmitt, C.A. Oncogene-Induced Senescence as an Initial Barrier in Lymphoma Development. Nature 2005, 436, 660–665. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.; Trotman, L.C.; Shaffer, D.; Lin, H.-K.; Dotan, Z.A.; Niki, M.; Koutcher, J.A.; Scher, H.I.; Ludwig, T.; Gerald, W.; et al. Crucial Role of P53-Dependent Cellular Senescence in Suppression of Pten-Deficient Tumorigenesis. Nature 2005, 436, 725–730. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Michaloglou, C.; Vredeveld, L.C.W.; Soengas, M.S.; Denoyelle, C.; Kuilman, T.; Van Der Horst, C.M.A.M.; Majoor, D.M.; Shay, J.W.; Mooi, W.J.; Peeper, D.S. BRAFE600-Associated Senescence-like Cell Cycle Arrest of Human Naevi. Nature 2005, 436, 720–724. [Google Scholar] [CrossRef]
- Aird, K.M.; Zhang, G.; Li, H.; Tu, Z.; Bitler, B.G.; Garipov, A.; Wu, H.; Wei, Z.; Wagner, S.N.; Herlyn, M.; et al. Suppression of Nucleotide Metabolism Underlies the Establishment and Maintenance of Oncogene-Induced Senescence. Cell Rep. 2013, 3, 1252–1265. [Google Scholar] [CrossRef] [Green Version]
- Böhme, I.; Bosserhoff, A. Extracellular Acidosis Triggers a Senescence-like Phenotype in Human Melanoma Cells. Pigment Cell Melanoma Res. 2020, 33, 41–51. [Google Scholar] [CrossRef] [Green Version]
- Nassour, J.; Martien, S.; Martin, N.; Deruy, E.; Tomellini, E.; Malaquin, N.; Bouali, F.; Sabatier, L.; Wernert, N.; Pinte, S.; et al. Defective {DNA} Single-Strand Break Repair Is Responsible for Senescence and Neoplastic Escape of Epithelial Cells. Nat. Commun. 2016, 7, 10399. [Google Scholar] [CrossRef] [Green Version]
- Gosselin, K.; Martien, S.; Pourtier, A.; Vercamer, C.; Ostoich, P.; Morat, L.; Sabatier, L.; Duprez, L.; de Roodenbeke, C.; Gilson, E.; et al. Senescence-Associated Oxidative {DNA} Damage Promotes the Generation of Neoplastic Cells. Cancer Res. 2009, 69, 7917–7925. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brenner, A.J.; Stampfer, M.R.; Aldaz, C.M. Increased P16 Expression with First Senescence Arrest in Human Mammary Epithelial Cells and Extended Growth Capacity with P16 Inactivation. Oncogene 1998, 17, 199–205. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jang, D.H.; Bhawal, U.K.; Min, H.K.; Kang, H.K.; Abiko, Y.; Min, B.M. A Transcriptional Roadmap to the Senescence and Differentiation of Human Oral Keratinocytes. J. Gerontol.-Ser. A Biol. Sci. Med. Sci. 2015, 70, 20–32. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rheinwald, J.G.; Hahn, W.C.; Ramsey, M.R.; Wu, J.Y.; Guo, Z.; Tsao, H.; De Luca, M.; Catricalà, C.; O’Toole, K.M. A Two-Stage, P16 INK4A-and P53-Dependent Keratinocyte Senescence Mechanism That Limits Replicative Potential Independent of Telomere Status. Mol. Cell. Biol. 2002, 22, 5157–5172. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Feijoo, P.; Terradas, M.; Soler, D.; Domínguez, D.; Tusell, L.; Genescà, A. Breast Primary Epithelial Cells That Escape P16-Dependent Stasis Enter a Telomeredriven Crisis State. Breast Cancer Res. 2016, 18, 7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Martin, N.; Cardozo, C.S.; Vercamer, C.; Ott, L.; Marot, G.; Slijepcevic, P.; Abbadie, C.; Pluquet, O. Identification of a Gene Signature of a Pre-Transformation Process by Senescence Evasion in Normal Human Epidermal Keratinocytes. Mol. Cancer 2014, 13, 151. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gosselin, K.; Deruy, E.; Martien, S.; Vercamer, C.; Bouali, F.; Dujardin, T.; Slomianny, C.; Houel-Renault, L.; Chelli, F.; De Launoit, Y.; et al. Senescent Keratinocytes Die by Autophagic Programmed Cell Death. Am. J. Pathol. 2009, 174, 423–435. [Google Scholar] [CrossRef] [Green Version]
- Romanov, S.R.; Kozakiewicz, B.K.; Holst, C.R.; Stampfer, M.R.; Haupt, L.M.; Tlsty, T.D. Normal Human Mammary Epithelial Cells Spontaneously Escape Senescence and Acquire Genomic Changes. Nature 2001, 409, 633–637. [Google Scholar] [CrossRef]
- Novak, P.; Jensen, T.J.; Garbe, J.C.; Stampfer, M.R.; Futscher, B.W. Stepwise DNA Methylation Changes Are Linked to Escape from Defined Proliferation Barriers and Mammary Epithelial Cell Immortalization. Cancer Res. 2009, 69, 5251–5258. [Google Scholar] [CrossRef] [Green Version]
- Tamayo-Orrego, L.; Wu, C.-L.; Bouchard, N.; Khedher, A.; Swikert, S.M.; Remke, M.; Skowron, P.; Taylor, M.D.; Charron, F. Evasion of Cell Senescence Leads to Medulloblastoma Progression. Cell Rep. 2016, 14, 2925–2937. [Google Scholar] [CrossRef] [Green Version]
- Shain, A.H.; Yeh, I.; Kovalyshyn, I.; Sriharan, A.; Talevich, E.; Gagnon, A.; Dummer, R.; North, J.; Pincus, L.; Ruben, B.; et al. The Genetic Evolution of Melanoma from Precursor Lesions. N. Engl. J. Med. 2015, 373, 1926–1936. [Google Scholar] [CrossRef]
- Bernstein, D.L.; Le Lay, J.E.; Ruano, E.G.; Kaestner, K.H. TALE-Mediated Epigenetic Suppression of CDKN2A Increases Replication in Human Fibroblasts. J. Clin. Investig. 2015, 125, 1998–2006. [Google Scholar] [CrossRef]
- Morel, A.P.; Lievre, M.; Thomas, C.; Hinkal, G.; Ansieau, S.; Puisieux, A. Generation of Breast Cancer Stem Cells through Epithelial-Mesenchymal Transition. PLoS ONE 2008, 3, e2888. [Google Scholar] [CrossRef]
- Mani, S.A.; Guo, W.; Liao, M.-J.J.; Eaton, E.N.; Ayyanan, A.; Zhou, A.Y.; Brooks, M.; Reinhard, F.; Zhang, C.C.; Shipitsin, M.; et al. The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells. Cell 2008, 133, 704–715. [Google Scholar] [CrossRef] [Green Version]
- Kumar, M.; Jaiswal, R.K.; Prasad, R.; Yadav, S.S.; Kumar, A.; Yadava, P.K.; Singh, R.P. PARP-1 Induces EMT in Non-Small Cell Lung Carcinoma Cells via Modulating the Transcription Factors Smad4, P65 and ZEB1. Life Sci. 2021, 269, 118994. [Google Scholar] [CrossRef]
- Pu, H.; Horbinski, C.; Hensley, P.J.; Matuszak, E.A.; Atkinson, T.; Kyprianou, N. PARP-1 Regulates Epithelial-Mesenchymal Transition (EMT) in Prostate Tumorigenesis. Carcinogenesis 2014, 35, 2592–2601. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rodríguez, M.I.; González-Flores, A.; Dantzer, F.; Collard, J.; De Herreros, A.G.; Oliver, F.J. Poly(ADP-Ribose)-Dependent Regulation of Snail1 Protein Stability. Oncogene 2011, 30, 4365–4372. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Serrano, M.; Lin, A.W.; McCurrach, M.E.; Beach, D.; Lowe, S.W. Oncogenic Ras Provokes Premature Cell Senescence Associated with Accumulation of P53 and P16(INK4a). Cell 1997, 88, 593–602. [Google Scholar] [CrossRef] [Green Version]
- Meeker, A.K.; Argani, P. Telomere Shortening Occurs Early during Breast Tumorigenesis: A Cause of Chromosome Destabilization Underlying Malignant Transformation? J. Mammary Gland Biol. Neoplasia 2004, 9, 285–296. [Google Scholar] [CrossRef] [PubMed]
- Castro-Vega, L.J.; Jouravleva, K.; Liu, W.-Y.; Martinez, C.; Gestraud, P.; Hupé, P.; Servant, N.; Albaud, B.; Gentien, D.; Gad, S.; et al. Telomere Crisis in Kidney Epithelial Cells Promotes the Acquisition of a MicroRNA Signature Retrieved in Aggressive Renal Cell Carcinomas. Carcinogenesis 2013, 34, 1173–1180. [Google Scholar] [CrossRef]
- Kuznetsova, A.Y.; Seget, K.; Moeller, G.K.; de Pagter, M.S.; de Roos, J.A.D.M.; Dürrbaum, M.; Kuffer, C.; Müller, S.; Zaman, G.J.R.; Kloosterman, W.P.; et al. Chromosomal Instability, Tolerance of Mitotic Errors and Multidrug Resistance Are Promoted by Tetraploidization in Human Cells. Cell Cycle 2015, 14, 2810–2820. [Google Scholar] [CrossRef]
- Galanos, P.; Vougas, K.; Walter, D.; Polyzos, A.; Maya-Mendoza, A.; Haagensen, E.J.; Kokkalis, A.; Roumelioti, F.-M.; Gagos, S.; Tzetis, M.; et al. Chronic P53-Independent P21 Expression Causes Genomic Instability by Deregulating Replication Licensing. Nat. Cell Biol. 2016, 18, 777–789. [Google Scholar] [CrossRef]
- Komseli, E.-S.; Pateras, I.S.; Krejsgaard, T.; Stawiski, K.; Rizou, S.V.; Polyzos, A.; Roumelioti, F.-M.; Chiourea, M.; Mourkioti, I.; Paparouna, E.; et al. A Prototypical Non-Malignant Epithelial Model to Study Genome Dynamics and Concurrently Monitor Micro-RNAs and Proteins in Situ during Oncogene-Induced Senescence. BMC Genom. 2018, 19, 37. [Google Scholar] [CrossRef] [Green Version]
- Zampetidis, C.; Galanos, P.; Angelopoulou, A.; Zhu, Y.; Karamitros, T.; Polyzou, A.; Mourkioti, I.; Lagopati, N.; Mirzazadeh, R.; Polyzos, A.; et al. Genomic Instability Is an Early Event Driving Chromatin Reorganization and Escape from Oncogene-Induced Senescence. bioRxiv 2020. [Google Scholar] [CrossRef]
- Matsumoto, T.; Wakefield, L.; Peters, A.; Peto, M.; Spellman, P.; Grompe, M. Proliferative Polyploid Cells Give Rise to Tumors via Ploidy Reduction. Nat. Commun. 2021, 12, 646. [Google Scholar] [CrossRef]
- Fujiwara, T.; Bandi, M.; Nitta, M.; Ivanova, E.V.; Bronson, R.T.; Pellman, D. Cytokinesis Failure Generating Tetraploids Promotes Tumorigenesis in P53-Null Cells. Nature 2005, 437, 1043–1047. [Google Scholar] [CrossRef] [PubMed]
- Davoli, T.; de Lange, T. Telomere-Driven Tetraploidization Occurs in Human Cells Undergoing Crisis and Promotes Transformation of Mouse Cells. Cancer Cell 2012, 21, 765–776. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zheng, L.; Dai, H.; Zhou, M.; Li, X.; Liu, C.; Guo, Z.; Wu, X.; Wu, J.; Wang, C.; Zhong, J.; et al. Polyploid Cells Rewire DNA Damage Response Networks to Overcome Replication Stress-Induced Barriers for Tumour Progression. Nat. Commun. 2012, 3, 815. [Google Scholar] [CrossRef] [PubMed]
- Leikam, C.; Hufnagel, A.L.; Otto, C.; Murphy, D.J.; Mühling, B.; Kneitz, S.; Nanda, I.; Schmid, M.; Wagner, T.U.; Haferkamp, S.; et al. In Vitro Evidence for Senescent Multinucleated Melanocytes as a Source for Tumor-Initiating Cells. Cell Death Dis. 2015, 6, e1711. [Google Scholar] [CrossRef] [Green Version]
- Lin, H.; Huang, Y.-S.; Fustin, J.-M.; Doi, M.; Chen, H.; Lai, H.-H.; Lin, S.-H.; Lee, Y.-L.; King, P.-C.; Hou, H.-S.; et al. Hyperpolyploidization of Hepatocyte Initiates Preneoplastic Lesion Formation in the Liver. Nat. Commun. 2021, 12, 645. [Google Scholar] [CrossRef]
- He, Q.; Au, B.; Kulkarni, M.; Shen, Y.; Lim, K.J.; Maimaiti, J.; Wong, C.K.; Luijten, M.N.H.; Chong, H.C.; Lim, E.H.; et al. Chromosomal Instability-Induced Senescence Potentiates Cell Non-Autonomous Tumourigenic Effects. Oncogenesis 2018, 7, 32. [Google Scholar] [CrossRef] [Green Version]
- Rajaraman, R.; Guernsey, D.L.; Rajaraman, M.M.; Rajaraman, S.R. Stem Cells, Senescence, Neosis and Self-Renewal in Cancer. Cancer Cell Int. 2006, 6, 25. [Google Scholar] [CrossRef] [Green Version]
- Walen, K.H. Spontaneous Cell Transformation: Karyoplasts Derived from Multinucleated Cells Produce New Cell Growth in Senescent Human Epithelial Cell Cultures. Vitr. Cell. Dev. Biol.-Anim. 2004, 40, 150–158. [Google Scholar] [CrossRef]
- Sundaram, M.; Guernsey, D.L.; Rajaraman, M.M.; Rajaraman, R. Neosis: A Novel Type of Cell Division in Cancer. Cancer Biol. Ther. 2004, 3, 207–218. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, S.; Mercado-Uribe, I.; Sood, A.; Bast, R.C.; Liu, J. Coevolution of Neoplastic Epithelial Cells and Multilineage Stroma via Polyploid Giant Cells during Immortalization and Transformation of Mullerian Epithelial Cells. Genes Cancer 2016, 7, 60–72. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Erenpreisa, J.A.; Cragg, M.S.; Fringes, B.; Sharakhov, I.; Illidge, T.M. Release of Mitotic Descendants by Giant Cells from Irradiated Burkitt’s Lymphoma Cell Line. Cell Biol. Int. 2000, 24, 635–648. [Google Scholar] [CrossRef]
- Illidge, T.M.; Cragg, M.S.; Fringes, B.; Olive, P.; Erenpreisa, J.A. Polyploid Giant Cells Provide a Survival Mechanism for P53 Mutant Cells after {DNA} Damage. Cell Biol. Int. 2000, 24, 621–633. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Erenpreisa, J.; Cragg, M.S. Three Steps to the Immortality of Cancer Cells: Senescence, Polyploidy and Self-Renewal. Cancer Cell Int. 2013, 13, 92. [Google Scholar] [CrossRef] [Green Version]
- Díaz-Carballo, D.; Gustmann, S.; Jastrow, H.; Acikelli, A.H.; Dammann, P.; Klein, J.; Dembinski, U.; Bardenheuer, W.; Malak, S.; Araúzo-Bravo, M.J.; et al. Atypical Cell Populations Associated with Acquired Resistance to Cytostatics and Cancer Stem Cell Features: The Role of Mitochondria in Nuclear Encapsulation. DNA Cell Biol. 2014, 33, 749–774. [Google Scholar] [CrossRef] [Green Version]
- Huna, A.; Salmina, K.; Jascenko, E.; Duburs, G.; Inashkina, I.; Erenpreisa, J. Self-Renewal Signalling in Presenescent Tetraploid IMR90 Cells. J. Aging Res. 2011, 2011, 103253. [Google Scholar] [CrossRef] [Green Version]
- Niu, N.; Mercado-Uribe, I.; Liu, J. Dedifferentiation into Blastomere-like Cancer Stem Cells via Formation of Polyploid Giant Cancer Cells. Oncogene 2017, 36, 4887–4900. [Google Scholar] [CrossRef] [Green Version]
- Liu, J. The Dualistic Origin of Human Tumors. Semin. Cancer Biol. 2018, 53, 1–16. [Google Scholar] [CrossRef]
- Lapasset, L.; Milhavet, O.; Prieur, A.; Besnard, E.; Babled, A.; Aït-Hamou, N.; Leschik, J.; Pellestor, F.; Ramirez, J.-M.; De Vos, J.; et al. Rejuvenating Senescent and Centenarian Human Cells by Reprogramming through the Pluripotent State. Genes Dev. 2011, 25, 2248–2253. [Google Scholar] [CrossRef] [Green Version]
- Nicaise, A.M.; Wagstaff, L.J.; Willis, C.M.; Paisie, C.; Chandok, H.; Robson, P.; Fossati, V.; Williams, A.; Crocker, S.J. Cellular Senescence in Progenitor Cells Contributes to Diminished Remyelination Potential in Progressive Multiple Sclerosis. Proc. Natl. Acad. Sci. USA 2019, 116, 9030–9039. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhu, P.; Zhang, C.; Gao, Y.; Wu, F.; Zhou, Y.; Wu, W.-S. The Transcription Factor Slug Represses P16Ink4a and Regulates Murine Muscle Stem Cell Aging. Nat. Commun. 2019, 10, 2568. [Google Scholar] [CrossRef] [PubMed]
- Ohashi, S.; Natsuizaka, M.; Wong, G.S.; Michaylira, C.Z.; Grugan, K.D.; Stairs, D.B.; Kalabis, J.; Vega, M.E.; Kalman, R.A.; Nakagawa, M.; et al. Epidermal Growth Factor Receptor and Mutant P53 Expand an Esophageal Cellular Subpopulation Capable of Epithelial-to-Mesenchymal Transition through ZEB Transcription Factors. Cancer Res. 2010, 70, 4174–4184. [Google Scholar] [CrossRef] [Green Version]
- Morel, A.-P.; Ginestier, C.; Pommier, R.M.; Cabaud, O.; Ruiz, E.; Wicinski, J.; Devouassoux-Shisheboran, M.; Combaret, V.; Finetti, P.; Chassot, C.; et al. A Stemness-Related ZEB1-MSRB3 Axis Governs Cellular Pliancy and Breast Cancer Genome Stability. Nat. Med. 2017, 23, 568–578. [Google Scholar] [CrossRef]
- Pommier, R.M.; Sanlaville, A.; Tonon, L.; Kielbassa, J.; Thomas, E.; Ferrari, A.; Sertier, A.S.; Hollande, F.; Martinez, P.; Tissier, A.; et al. Comprehensive Characterization of Claudin-Low Breast Tumors Reflects the Impact of the Cell-of-Origin on Cancer Evolution. Nat. Commun. 2020, 11, 3431. [Google Scholar] [CrossRef] [PubMed]
- Visvader, J.E. Cells of Origin in Cancer. Nature 2011, 469, 314–322. [Google Scholar] [CrossRef]
- Chen, X.; Pappo, A.; Dyer, M.A. Pediatric Solid Tumor Genomics and Developmental Pliancy. Oncogene 2015, 34, 5207–5215. [Google Scholar] [CrossRef] [Green Version]
- Coppé, J.P.; Patil, C.K.; Rodier, F.; Sun, Y.; Muñoz, D.P.; Goldstein, J.; Nelson, P.S.; Desprez, P.Y.; Campisi, J. Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the P53 Tumor Suppressor. PLoS Biol. 2008, 6, e301. [Google Scholar] [CrossRef]
- Ohanna, M.; Giuliano, S.; Bonet, C.; Imbert, V.; Hofman, V.; Zangari, J.; Bille, K.; Robert, C.; Bressac-de Paillerets, B.; Hofman, P.; et al. Senescent Cells Develop a PARP-1 and Nuclear Factor-KappaB-Associated Secretome (PNAS). Genes Dev. 2011, 25, 1245–1261. [Google Scholar] [CrossRef] [Green Version]
- Coppé, J.-P.; Rodier, F.; Patil, C.K.; Freund, A.; Desprez, P.-Y.; Campisi, J. Tumor Suppressor and Aging Biomarker P16(INK4a) Induces Cellular Senescence without the Associated Inflammatory Secretory Phenotype. J. Biol. Chem. 2011, 286, 36396–36403. [Google Scholar] [CrossRef] [Green Version]
- Laberge, R.M.; Sun, Y.; Orjalo, A.V.; Patil, C.K.; Freund, A.; Zhou, L.; Curran, S.C.; Davalos, A.R.; Wilson-Edell, K.A.; Liu, S.; et al. MTOR Regulates the Pro-Tumorigenic Senescence-Associated Secretory Phenotype by Promoting IL1A Translation. Nat. Cell Biol. 2015, 17, 1049–1061. [Google Scholar] [CrossRef]
- Wiley, C.D.; Velarde, M.C.; Lecot, P.; Liu, S.; Sarnoski, E.A.; Freund, A.; Shirakawa, K.; Lim, H.W.; Davis, S.S.; Ramanathan, A.; et al. Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype. Cell Metab. 2016, 23, 303–314. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Basisty, N.; Kale, A.; Jeon, O.H.; Kuehnemann, C.; Payne, T.; Rao, C.; Holtz, A.; Shah, S.; Sharma, V.; Ferrucci, L.; et al. A Proteomic Atlas of Senescence-Associated Secretomes for Aging Biomarker Development. PLoS Biol. 2020, 18, e3000599. [Google Scholar] [CrossRef] [Green Version]
- Glück, S.; Guey, B.; Gulen, M.F.; Wolter, K.; Kang, T.-W.; Schmacke, N.A.; Bridgeman, A.; Rehwinkel, J.; Zender, L.; Ablasser, A. Innate Immune Sensing of Cytosolic Chromatin Fragments through CGAS Promotes Senescence. Nat. Cell Biol. 2017, 19, 1061–1070. [Google Scholar] [CrossRef]
- Freund, A.; Patil, C.K.; Campisi, J. P38MAPK Is a Novel DNA Damage Response-Independent Regulator of the Senescence-Associated Secretory Phenotype. EMBO J. 2011, 30, 1536–1548. [Google Scholar] [CrossRef] [Green Version]
- Dou, Z.; Ghosh, K.; Vizioli, M.G.; Zhu, J.; Sen, P.; Wangensteen, K.J.; Simithy, J.; Lan, Y.; Lin, Y.; Zhou, Z.; et al. Cytoplasmic Chromatin Triggers Inflammation in Senescence and Cancer. Nature 2017, 550, 402–406. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takahashi, A.; Loo, T.M.; Okada, R.; Kamachi, F.; Watanabe, Y.; Wakita, M.; Watanabe, S.; Kawamoto, S.; Miyata, K.; Barber, G.N.; et al. Downregulation of Cytoplasmic DNases Is Implicated in Cytoplasmic DNA Accumulation and SASP in Senescent Cells. Nat. Commun. 2018, 9, 1249. [Google Scholar] [CrossRef] [PubMed]
- Yang, H.; Wang, H.; Ren, J.; Chen, Q.; Chen, Z.J. CGAS Is Essential for Cellular Senescence. Proc. Natl. Acad. Sci. USA 2017, 114, E4612–E4620. [Google Scholar] [CrossRef] [Green Version]
- Wang, B.; Brandenburg, S.; Hernandez-Segura, A.; van Vliet, T.; Jongbloed, E.M.; Wilting, S.M.; Ohtani, N.; Jager, A.; Demaria, M. Pharmacological CDK4/6 Inhibition Unravels a P53-Induced Secretory Phenotype in Senescent Cells. bioRxiv 2020. [Google Scholar] [CrossRef]
- Mosteiro, L.; Pantoja, C.; de Martino, A.; Serrano, M. Senescence Promotes in Vivo Reprogramming through P16 INK4a and IL-6. Aging Cell 2018, 17, e12711. [Google Scholar] [CrossRef] [PubMed]
- Ohnishi, K.; Semi, K.; Yamamoto, T.; Shimizu, M.; Tanaka, A.; Mitsunaga, K.; Okita, K.; Osafune, K.; Arioka, Y.; Maeda, T.; et al. Premature Termination of Reprogramming in Vivo Leads to Cancer Development through Altered Epigenetic Regulation. Cell 2014, 156, 663–677. [Google Scholar] [CrossRef] [Green Version]
- Iglesias, J.M.; Gumuzio, J.; Martin, A.G. Linking Pluripotency Reprogramming and Cancer. Stem Cells Transl. Med. 2017, 6, 335–339. [Google Scholar] [CrossRef]
- Ahn, J.; Xia, T.; Konno, H.; Konno, K.; Ruiz, P.; Barber, G.N. Inflammation-Driven Carcinogenesis Is Mediated through STING. Nat. Commun. 2014, 5, 5166. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Malaquin, N.; Vercamer, C.; Bouali, F.; Martien, S.; Deruy, E.; Wernert, N.; Chwastyniak, M.; Pinet, F.; Abbadie, C.; Pourtier, A. Senescent Fibroblasts Enhance Early Skin Carcinogenic Events via a Paracrine MMP-PAR-1 Axis. PLoS ONE 2013, 8, e63607. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alimirah, F.; Pulido, T.; Valdovinos, A.; Alptekin, S.; Chang, E.; Jones, E.; Diaz, D.A.; Flores, J.; Velarde, M.C.; Demaria, M.; et al. Cellular Senescence Promotes Skin Carcinogenesis through P38MAPK and P44/42MAPK Signaling. Cancer Res. 2020, 80, 3606–3619. [Google Scholar] [CrossRef]
- Jun, J.-I.; Lau, L.F. Cellular Senescence Controls Fibrosis in Wound Healing. Aging (Albany NY) 2010, 2, 627–631. [Google Scholar] [CrossRef] [Green Version]
- Kang, T.-W.; Yevsa, T.; Woller, N.; Hoenicke, L.; Wuestefeld, T.; Dauch, D.; Hohmeyer, A.; Gereke, M.; Rudalska, R.; Potapova, A.; et al. Senescence Surveillance of Pre-Malignant Hepatocytes Limits Liver Cancer Development. Nature 2011, 479, 547–551. [Google Scholar] [CrossRef]
- Xue, W.; Zender, L.; Miething, C.; Dickins, R.A.; Hernando, E.; Krizhanovsky, V.; Cordon-Cardo, C.; Lowe, S.W. Senescence and Tumour Clearance Is Triggered by P53 Restoration in Murine Liver Carcinomas. Nature 2007, 445, 656–660. [Google Scholar] [CrossRef] [Green Version]
- Gonçalves, S.; Yin, K.; Ito, Y.; Chan, A.; Olan, I.; Gough, S.; Cassidy, L.; Serrao, E.; Smith, S.; Young, A.; et al. COX2 Regulates Senescence Secretome Composition and Senescence Surveillance through PGE2. Cell Rep. 2021, 34, 108860. [Google Scholar] [CrossRef]
- Lau, L.; David, G. Pro- and Anti-Tumorigenic Functions of the Senescence-Associated Secretory Phenotype. Expert Opin. Ther. Targets 2019, 23, 1041–1051. [Google Scholar] [CrossRef]
- Ortiz-Montero, P.; Londoño-Vallejo, A.; Vernot, J.P. Senescence-Associated IL-6 and IL-8 Cytokines Induce a Self- and Cross-Reinforced Senescence/Inflammatory Milieu Strengthening Tumorigenic Capabilities in the MCF-7 Breast Cancer Cell Line. Cell Commun. Signal. 2017, 15, 17. [Google Scholar] [CrossRef] [Green Version]
- Vernot, J.P. Senescence-Associated Pro-Inflammatory Cytokines and Tumor Cell Plasticity. Front. Mol. Biosci. 2020, 7, 63. [Google Scholar] [CrossRef]
- Lujambio, A.; Akkari, L.; Simon, J.; Grace, D.; Tschaharganeh, D.F.; Bolden, J.E.; Zhao, Z.; Thapar, V.; Joyce, J.A.; Krizhanovsky, V.; et al. Non-Cell-Autonomous Tumor Suppression by P53. Cell 2013, 153, 449–460. [Google Scholar] [CrossRef] [Green Version]
- Tasdemir, N.; Banito, A.; Roe, J.-S.; Alonso-Curbelo, D.; Camiolo, M.; Tschaharganeh, D.F.; Huang, C.-H.; Aksoy, O.; Bolden, J.E.; Chen, C.-C.; et al. BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance. Cancer Discov. 2016, 6, 612–629. [Google Scholar] [CrossRef] [Green Version]
- Iannello, A.; Thompson, T.W.; Ardolino, M.; Lowe, S.W.; Raulet, D.H. P53-Dependent Chemokine Production by Senescent Tumor Cells Supports NKG2D-Dependent Tumor Elimination by Natural Killer Cells. J. Exp. Med. 2013, 210, 2057–2069. [Google Scholar] [CrossRef]
- Krizhanovsky, V.; Yon, M.; Dickins, R.A.; Hearn, S.; Simon, J.; Miething, C.; Yee, H.; Zender, L.; Lowe, S.W. Senescence of Activated Stellate Cells Limits Liver Fibrosis. Cell 2008, 134, 657–667. [Google Scholar] [CrossRef] [Green Version]
- Sagiv, A.; Biran, A.; Yon, M.; Simon, J.; Lowe, S.W.; Krizhanovsky, V. Granule Exocytosis Mediates Immune Surveillance of Senescent Cells. Oncogene 2013, 32, 1971–1977. [Google Scholar] [CrossRef] [Green Version]
- Sagiv, A.; Burton, D.G.A.; Moshayev, Z.; Vadai, E.; Wensveen, F.; Ben-Dor, S.; Golani, O.; Polic, B.; Krizhanovsky, V. NKG2D Ligands Mediate Immunosurveillance of Senescent Cells. Aging (Albany NY) 2016, 8, 328–344. [Google Scholar] [CrossRef] [Green Version]
- Muñoz, D.P.; Yannone, S.M.; Daemen, A.; Sun, Y.; Vakar-Lopez, F.; Kawahara, M.; Freund, A.M.; Rodier, F.; Wu, J.D.; Desprez, P.-Y.; et al. Targetable Mechanisms Driving Immunoevasion of Persistent Senescent Cells Link Chemotherapy-Resistant Cancer to Aging. JCI Insight 2019, 4, e124716. [Google Scholar] [CrossRef] [Green Version]
- Pereira, B.I.; Devine, O.P.; Vukmanovic-Stejic, M.; Chambers, E.S.; Subramanian, P.; Patel, N.; Virasami, A.; Sebire, N.J.; Kinsler, V.; Valdovinos, A.; et al. Senescent Cells Evade Immune Clearance via HLA-E-Mediated NK and CD8+ T Cell Inhibition. Nat. Commun. 2019, 10, 2387. [Google Scholar] [CrossRef] [PubMed]
- Miranda, A.; Hamilton, P.T.; Zhang, A.W.; Pattnaik, S.; Becht, E.; Mezheyeuski, A.; Bruun, J.; Micke, P.; de Reynies, A.; Nelson, B.H. Cancer Stemness, Intratumoral Heterogeneity, and Immune Response across Cancers. Proc. Natl. Acad. Sci. USA 2019, 116, 9020–9029. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Paczulla, A.M.; Rothfelder, K.; Raffel, S.; Konantz, M.; Steinbacher, J.; Wang, H.; Tandler, C.; Mbarga, M.; Schaefer, T.; Falcone, M.; et al. Absence of {NKG}2D Ligands Defines Leukaemia Stem Cells and Mediates Their Immune Evasion. Nature 2019, 572, 254–259. [Google Scholar] [CrossRef] [PubMed]
- Agudo, J.; Park, E.S.; Rose, S.A.; Alibo, E.; Sweeney, R.; Dhainaut, M.; Kobayashi, K.S.; Sachidanandam, R.; Baccarini, A.; Merad, M.; et al. Quiescent Tissue Stem Cells Evade Immune Surveillance. Immunity 2018, 48, 271–285.e5. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Koebel, C.M.; Vermi, W.; Swann, J.B.; Zerafa, N.; Rodig, S.J.; Old, L.J.; Smyth, M.J.; Schreiber, R.D. Adaptive Immunity Maintains Occult Cancer in an Equilibrium State. Nature 2007, 450, 903–907. [Google Scholar] [CrossRef] [PubMed]
- Malladi, S.; Macalinao, D.G.; Jin, X.; He, L.; Basnet, H.; Zou, Y.; de Stanchina, E.; Massagué, J. Metastatic Latency and Immune Evasion through Autocrine Inhibition of WNT. Cell 2016, 165, 45–60. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Burr, M.L.; Sparbier, C.E.; Chan, K.L.; Chan, Y.-C.; Kersbergen, A.; Lam, E.Y.N.; Azidis-Yates, E.; Vassiliadis, D.; Bell, C.C.; Gilan, O.; et al. An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer. Cancer Cell 2019, 36, 385–401.e8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Laughney, A.M.; Hu, J.; Campbell, N.R.; Bakhoum, S.F.; Setty, M.; Lavallée, V.-P.; Xie, Y.; Masilionis, I.; Carr, A.J.; Kottapalli, S.; et al. Regenerative Lineages and Immune-Mediated Pruning in Lung Cancer Metastasis. Nat. Med. 2020, 26, 259–269. [Google Scholar] [CrossRef]
- Pommier, A.; Anaparthy, N.; Memos, N.; Kelley, Z.L.; Gouronnec, A.; Yan, R.; Auffray, C.; Albrengues, J.; Egeblad, M.; Iacobuzio-Donahue, C.A.; et al. Unresolved Endoplasmic Reticulum Stress Engenders Immune-Resistant, Latent Pancreatic Cancer Metastases. Science 2018, 360, 6394. [Google Scholar] [CrossRef] [Green Version]
- Terry, S.; Savagner, P.; Ortiz-Cuaran, S.; Mahjoubi, L.; Saintigny, P.; Thiery, J.-P.; Chouaib, S. New Insights into the Role of EMT in Tumor Immune Escape. Mol. Oncol. 2017, 11, 824–846. [Google Scholar] [CrossRef] [Green Version]
- Knutson, K.L.; Lu, H.; Stone, B.; Reiman, J.M.; Behrens, M.D.; Prosperi, C.M.; Gad, E.A.; Smorlesi, A.; Disis, M.L. Immunoediting of Cancers May Lead to Epithelial to Mesenchymal Transition. J. Immunol. 2006, 177, 1526–1533. [Google Scholar] [CrossRef]
- Eggert, T.; Wolter, K.; Ji, J.; Ma, C.; Yevsa, T.; Klotz, S.; Medina-Echeverz, J.; Longerich, T.; Forgues, M.; Reisinger, F.; et al. Distinct Functions of Senescence-Associated Immune Responses in Liver Tumor Surveillance and Tumor Progression. Cancer Cell 2016, 30, 533–547. [Google Scholar] [CrossRef] [Green Version]
- Hoechst, B.; Voigtlaender, T.; Ormandy, L.; Gamrekelashvili, J.; Zhao, F.; Wedemeyer, H.; Lehner, F.; Manns, M.P.; Greten, T.F.; Korangy, F. Myeloid Derived Suppressor Cells Inhibit Natural Killer Cells in Patients with Hepatocellular Carcinoma via the NKp30 Receptor. Hepatology 2009, 50, 799–807. [Google Scholar] [CrossRef]
- Elmore, L.W.; Di, X.; Dumur, C.; Holt, S.E.; Gewirtz, D.A. Evasion of a Single-Step, Chemotherapy-Induced Senescence in Breast Cancer Cells: Implications for Treatment Response. Clin. Cancer Res. 2005, 11, 2637–2643. [Google Scholar] [CrossRef] [Green Version]
- Roberson, R.S.; Kussick, S.J.; Vallieres, E.; Chen, S.-Y.J.; Wu, D.Y. Escape from Therapy-Induced Accelerated Cellular Senescence in P53-Null Lung Cancer Cells and in Human Lung Cancers. Cancer Res. 2005, 65, 2795–2803. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Walter, P.; Pusel, J.; Rousselot, P. Multinucleated Giant Cell Tumor of the Thyroid: An Unusual Anaplastic Carcinoma (Author’s Transl). Pathol. Res. Pract. 1980, 167, 402–409. [Google Scholar] [CrossRef]
- Douglas-Jones, A.G.; Barr, W.T. Breast Carcinoma with Tumor Giant Cells. Report of a Case with Fine Needle Aspiration Cytology. Acta. Cytol. 1989, 33, 109–114. [Google Scholar] [PubMed]
- Jones, M.A.; Young, R.H.; Scully, R.E. Endometrial Adenocarcinoma with a Component of Giant Cell Carcinoma. Int. J. Gynecol. Pathol. 1991, 10, 260–270. [Google Scholar] [CrossRef] [PubMed]
- Zack, T.I.; Schumacher, S.E.; Carter, S.L.; Cherniack, A.D.; Saksena, G.; Tabak, B.; Lawrence, M.S.; Zhsng, C.-Z.; Wala, J.; Mermel, C.H.; et al. Pan-Cancer Patterns of Somatic Copy Number Alteration. Nat. Genet. 2013, 45, 1134–1140. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bielski, C.M.; Zehir, A.; Penson, A.V.; Donoghue, M.T.A.; Chatila, W.; Armenia, J.; Chang, M.T.; Schram, A.M.; Jonsson, P.; Bandlamudi, C.; et al. Genome Doubling Shapes the Evolution and Prognosis of Advanced Cancers. Nat. Genet. 2018, 50, 1189–1195. [Google Scholar] [CrossRef]
- Zhang, S.; Mercado-Uribe, I.; Xing, Z.; Sun, B.; Kuang, J.; Liu, J. Generation of Cancer Stem-like Cells through the Formation of Polyploid Giant Cancer Cells. Oncogene 2014, 33, 116–128. [Google Scholar] [CrossRef]
- Mosieniak, G.; Sliwinska, M.A.; Alster, O.; Strzeszewska, A.; Sunderland, P.; Piechota, M.; Was, H.; Sikora, E. Polyploidy Formation in Doxorubicin-Treated Cancer Cells Can Favor Escape from Senescence. Neoplasia 2015, 17, 882–893. [Google Scholar] [CrossRef] [Green Version]
- Rohnalter, V.; Roth, K.; Finkernagel, F.; Adhikary, T.; Obert, J.; Dorzweiler, K.; Bensberg, M.; Müller-Brüsselbach, S.; Müller, R. A Multi-Stage Process Including Transient Polyploidization and EMT Precedes the Emergence of Chemoresistent Ovarian Carcinoma Cells with a Dedifferentiated and pro-Inflammatory Secretory Phenotype. Oncotarget 2015, 6, 40005–40025. [Google Scholar] [CrossRef] [PubMed]
- Puig, P.-E.; Guilly, M.-N.; Bouchot, A.; Droin, N.; Cathelin, D.; Bouyer, F.; Favier, L.; Ghiringhelli, F.; Kroemer, G.; Solary, E.; et al. Tumor Cells Can Escape DNA-Damaging Cisplatin through DNA Endoreduplication and Reversible Polyploidy. Cell Biol. Int. 2008, 32, 1031–1043. [Google Scholar] [CrossRef]
- Wang, Q.; Wu, P.C.; Dong, D.Z.; Ivanova, I.; Chu, E.; Zeliadt, S.; Vesselle, H.; Wu, D.Y. Polyploidy Road to Therapy-Induced Cellular Senescence and Escape. Int. J. Cancer 2013, 132, 1505–1515. [Google Scholar] [CrossRef]
- Fei, F.; Zhang, D.; Yang, Z.; Wang, S.; Wang, X.; Wu, Z.; Wu, Q.; Zhang, S. The Number of Polyploid Giant Cancer Cells and Epithelial-Mesenchymal Transition-Related Proteins Are Associated with Invasion and Metastasis in Human Breast Cancer. J. Exp. Clin. Cancer Res. 2015, 34, 158. [Google Scholar] [CrossRef] [Green Version]
- Salmina, K.; Jankevics, E.; Huna, A.; Perminov, D.; Radovica, I.; Klymenko, T.; Ivanov, A.; Jascenko, E.; Scherthan, H.; Cragg, M.; et al. Up-Regulation of the Embryonic Self-Renewal Network through Reversible Polyploidy in Irradiated P53-Mutant Tumour. Exp. Cell Res. 2010, 316, 2099–2112. [Google Scholar] [CrossRef] [PubMed]
- Lagadec, C.; Vlashi, E.; Della Donna, L.; Dekmezian, C.; Pajonk, F. Radiation-Induced Reprogramming of Breast Cancer Cells. Stem Cells 2012, 30, 833–844. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Weihua, Z.; Lin, Q.; Ramoth, A.J.; Fan, D.; Fidler, I.J. Formation of Solid Tumors by a Single Multinucleated Cancer Cell. Cancer 2011, 117, 4092–4099. [Google Scholar] [CrossRef] [Green Version]
- Milanovic, M.; Fan, D.N.Y.; Belenki, D.; Däbritz, J.H.M.; Zhao, Z.; Yu, Y.; Dörr, J.R.; Dimitrova, L.; Lenze, D.; Monteiro Barbosa, I.A.; et al. Senescence-Associated Reprogramming Promotes Cancer Stemness. Nature 2018, 553, 96–100. [Google Scholar] [CrossRef] [Green Version]
- Dewhurst, S.M.; McGranahan, N.; Burrell, R.A.; Rowan, A.J.; Grönroos, E.; Endesfelder, D.; Joshi, T.; Mouradov, D.; Gibbs, P.; Ward, R.L.; et al. Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution. Cancer Discov. 2014, 4, 175–185. [Google Scholar] [CrossRef] [Green Version]
- Salmina, K.; Bojko, A.; Inashkina, I.; Staniak, K.; Dudkowska, M.; Podlesniy, P.; Rumnieks, F.; Vainshelbaum, N.M.; Pjanova, D.; Sikora, E.; et al. “Mitotic Slippage” and Extranuclear DNA in Cancer Chemoresistance: A Focus on Telomeres. Int. J. Mol. Sci. 2020, 21, 2779. [Google Scholar] [CrossRef] [Green Version]
- Achuthan, S.; Santhoshkumar, T.R.; Prabhakar, J.; Nair, S.A.; Pillai, M.R. Drug-Induced Senescence Generates Chemoresistant Stemlike Cells with Low Reactive Oxygen Species. J. Biol. Chem. 2011, 286, 37813–37829. [Google Scholar] [CrossRef] [Green Version]
- Ge, J.Y.; Shu, S.; Kwon, M.; Jovanović, B.; Murphy, K.; Gulvady, A.; Fassl, A.; Trinh, A.; Kuang, Y.; Heavey, G.A.; et al. Acquired Resistance to Combined BET and CDK4/6 Inhibition in Triple-Negative Breast Cancer. Nat. Commun. 2020, 11, 2350. [Google Scholar] [CrossRef] [PubMed]
- Duy, C.; Li, M.; Teater, M.; Meydan, C.; Garrett-Bakelman, F.E.; Lee, T.C.; Chin, C.R.; Durmaz, C.; Kawabata, K.C.; Dhimolea, E.; et al. Chemotherapy Induces Senescence-like Resilient Cells Capable of Initiating AML Recurrence. Cancer Discov. 2021, 11, 1542–1561. [Google Scholar] [CrossRef]
- Iliopoulos, D.; Hirsch, H.A.; Struhl, K. An Epigenetic Switch Involving NF-KappaB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation. Cell 2009, 139, 693–706. [Google Scholar] [CrossRef] [Green Version]
- Iliopoulos, D.; Hirsch, H.A.; Wang, G.; Struhl, K. Inducible Formation of Breast Cancer Stem Cells and Their Dynamic Equilibrium with Non-Stem Cancer Cells via IL6 Secretion. Proc. Natl. Acad. Sci. USA 2011, 108, 1397–1402. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mitra, A.; Yan, J.; Xia, X.; Zhou, S.; Chen, J.; Mishra, L.; Li, S. IL6-Mediated Inflammatory Loop Reprograms Normal to Epithelial-Mesenchymal Transition+ Metastatic Cancer Stem Cells in Preneoplastic Liver of Transforming Growth Factor Beta-Deficient Β2-Spectrin+/- Mice. Hepatology 2017, 65, 1222–1236. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cruickshanks, H.A.; McBryan, T.; Nelson, D.M.; Vanderkraats, N.D.; Shah, P.P.; van Tuyn, J.; Singh Rai, T.; Brock, C.; Donahue, G.; Dunican, D.S.; et al. Senescent Cells Harbour Features of the Cancer Epigenome. Nat. Cell Biol. 2013, 15, 1495–1506. [Google Scholar] [CrossRef]
- Canino, C.; Mori, F.; Cambria, A.; Diamantini, A.; Germoni, S.; Alessandrini, G.; Borsellino, G.; Galati, R.; Battistini, L.; Blandino, R.; et al. SASP Mediates Chemoresistance and Tumor-Initiating-Activity of Mesothelioma. Oncogene 2012, 31, 3148–3163. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cahu, J.; Bustany, S.; Sola, B. Senescence-Associated Secretory Phenotype Favors the Emergence of Cancer Stem-like Cells. Cell Death Dis. 2012, 3, e446. [Google Scholar] [CrossRef]
- Mackenzie, K.J.; Carroll, P.; Martin, C.-A.; Murina, O.; Fluteau, A.; Simpson, D.J.; Olova, N.; Sutcliffe, H.; Rainger, J.K.; Leitch, A.; et al. CGAS Surveillance of Micronuclei Links Genome Instability to Innate Immunity. Nature 2017, 548, 461–465. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Demaria, M.; O’Leary, M.N.; Chang, J.; Shao, L.; Liu, S.; Alimirah, F.; Koenig, K.; Le, C.; Mitin, N.; Deal, A.M.; et al. Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse. Cancer Discov. 2017, 7, 165–176. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, Y.H.; Choi, Y.W.; Lee, J.; Soh, E.Y.; Kim, J.-H.; Park, T.J. Senescent Tumor Cells Lead the Collective Invasion in Thyroid Cancer. Nat. Commun. 2017, 8, 15208. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bakhoum, S.F.; Ngo, B.; Laughney, A.M.; Cavallo, J.-A.; Murphy, C.J.; Ly, P.; Shah, P.; Sriram, R.K.; Watkins, T.B.K.; Taunk, N.K.; et al. Chromosomal Instability Drives Metastasis through a Cytosolic DNA Response. Nature 2018, 553, 467–472. [Google Scholar] [CrossRef] [Green Version]
- Braumüller, H.; Wieder, T.; Brenner, E.; Aßmann, S.; Hahn, M.; Alkhaled, M.; Schilbach, K.; Essmann, F.; Kneilling, M.; Griessinger, C.; et al. T-Helper-1-Cell Cytokines Drive Cancer into Senescence. Nature 2013, 494, 361–365. [Google Scholar] [CrossRef] [Green Version]
- Sarkisian, C.J.; Keister, B.A.; Stairs, D.B.; Boxer, R.B.; Moody, S.E.; Chodosh, L.A. Dose-Dependent Oncogene-Induced Senescence in Vivo and Its Evasion during Mammary Tumorigenesis. Nat. Cell Biol. 2007, 9, 493–505. [Google Scholar] [CrossRef] [PubMed]
- Roninson, I.B.; Broude, E.V.; Chang, B.-D. If Not Apoptosis, Then What? Treatment-Induced Senescence and Mitotic Catastrophe in Tumor Cells. Drug Resist. Updates 2001, 4, 303–313. [Google Scholar] [CrossRef]
- Soriani, A.; Zingoni, A.; Cerboni, C.; Iannitto, M.L.; Ricciardi, M.R.; Di Gialleonardo, V.; Cippitelli, M.; Fionda, C.; Petrucci, M.T.; Guarini, A.; et al. ATM-ATR-Dependent up-Regulation of DNAM-1 and NKG2D Ligands on Multiple Myeloma Cells by Therapeutic Agents Results in Enhanced NK-Cell Susceptibility and Is Associated with a Senescent Phenotype. Blood 2009, 113, 3503–3511. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Antonangeli, F.; Soriani, A.; Ricci, B.; Ponzetta, A.; Benigni, G.; Morrone, S.; Bernardini, G.; Santoni, A. Natural Killer Cell Recognition of in Vivo Drug-Induced Senescent Multiple Myeloma Cells. Oncoimmunology 2016, 5, e1218105. [Google Scholar] [CrossRef] [Green Version]
- Nguyen, H.Q.; To, N.H.; Zadigue, P.; Kerbrat, S.; De La Taille, A.; Le Gouvello, S.; Belkacemi, Y. Ionizing Radiation-Induced Cellular Senescence Promotes Tissue Fibrosis after Radiotherapy. A Review. Crit. Rev. Oncol. Hematol. 2018, 129, 13–26. [Google Scholar] [CrossRef]
- Chen, J.; Li, Y.; Yu, T.S.; McKay, R.M.; Burns, D.K.; Kernie, S.G.; Parada, L.F. A Restricted Cell Population Propagates Glioblastoma Growth after Chemotherapy. Nature 2012, 488, 522–526. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kobayashi, S.; Yamada-Okabe, H.; Suzuki, M.; Natori, O.; Kato, A.; Matsubara, K.; Jau Chen, Y.; Yamazaki, M.; Funahashi, S.; Yoshida, K.; et al. LGR5-Positive Colon Cancer Stem Cells Interconvert with Drug-Resistant LGR5-Negative Cells and Are Capable of Tumor Reconstitution. Stem Cells 2012, 30, 2631–2644. [Google Scholar] [CrossRef] [PubMed]
- Essers, M.A.G.; Offner, S.; Blanco-Bose, W.E.; Waibler, Z.; Kalinke, U.; Duchosal, M.A.; Trumpp, A. IFNalpha Activates Dormant Haematopoietic Stem Cells in Vivo. Nature 2009, 458, 904–908. [Google Scholar] [CrossRef]
- Kreso, A.; O’Brien, C.A.; van Galen, P.; Gan, O.I.; Notta, F.; Brown, A.M.K.; Ng, K.; Ma, J.; Wienholds, E.; Dunant, C.; et al. Variable Clonal Repopulation Dynamics Influence Chemotherapy Response in Colorectal Cancer. Science 2013, 339, 543–548. [Google Scholar] [CrossRef] [Green Version]
- Chockley, P.J.; Chen, J.; Chen, G.; Beer, D.G.; Standiford, T.J.; Keshamouni, V.G. Epithelial-Mesenchymal Transition Leads to {NK} Cell-Mediated Metastasis-Specific Immunosurveillance in Lung Cancer. J. Clin. Investig. 2018, 128, 1384–1396. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Su, S.; Liu, Q.; Chen, J.; Chen, J.; Chen, F.; He, C.; Huang, D.; Wu, W.; Lin, L.; Huang, W.; et al. A Positive Feedback Loop between Mesenchymal-like Cancer Cells and Macrophages Is Essential to Breast Cancer Metastasis. Cancer Cell 2014, 25, 605–620. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ouzounova, M.; Lee, E.; Piranlioglu, R.; El Andaloussi, A.; Kolhe, R.; Demirci, M.F.; Marasco, D.; Asm, I.; Chadli, A.; Hassan, K.A.; et al. Monocytic and Granulocytic Myeloid Derived Suppressor Cells Differentially Regulate Spatiotemporal Tumour Plasticity during Metastatic Cascade. Nat. Commun. 2017, 8, 14979. [Google Scholar] [CrossRef] [PubMed]
- Perkins, D.W.; Haider, S.; Robertson, D.; Buus, R.; O’Leary, L.; Isacke, C.M. Therapy-Induced Senescence in Normal Tissue Promotes Breast Cancer Metastasis. bioRxiv 2020. [Google Scholar] [CrossRef]
- Coppe, J.P.; Kauser, K.; Campisi, J.; Beauséjour, C.M. Secretion of Vascular Endothelial Growth Factor by Primary Human Fibroblasts at Senescence. J. Biol. Chem. 2006, 281, 29568–29574. [Google Scholar] [CrossRef] [Green Version]
Type of SASP | Secreted Factors |
---|---|
NF-KB-dependent inflammatory-type SASP | IL1α, Ilβ, IL6, IL8, IL10, CXCL1, CXCL2, VEGF, MMP3, TNFα, FGF |
p53-dependent SASP | GRO, GROα, IGFBP3, LIF, IL6, IL8, CCL2, CCL17, Leptin, ISG15, GDF15, TGFα |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
De Blander, H.; Morel, A.-P.; Senaratne, A.P.; Ouzounova, M.; Puisieux, A. Cellular Plasticity: A Route to Senescence Exit and Tumorigenesis. Cancers 2021, 13, 4561. https://doi.org/10.3390/cancers13184561
De Blander H, Morel A-P, Senaratne AP, Ouzounova M, Puisieux A. Cellular Plasticity: A Route to Senescence Exit and Tumorigenesis. Cancers. 2021; 13(18):4561. https://doi.org/10.3390/cancers13184561
Chicago/Turabian StyleDe Blander, Hadrien, Anne-Pierre Morel, Aruni P. Senaratne, Maria Ouzounova, and Alain Puisieux. 2021. "Cellular Plasticity: A Route to Senescence Exit and Tumorigenesis" Cancers 13, no. 18: 4561. https://doi.org/10.3390/cancers13184561