CAF-Associated Genes in Breast Cancer for Novel Therapeutic Strategies
Abstract
:1. Introduction
2. CAFs Classification and Heterogeneity in BC
3. Material and Methods
3.1. Expression Profiles of the Microdissection Tissues of the 28 BC Tumors (GSE10797)
3.2. Statistical Analysis
4. BC CAFGs and Current Understanding Its Functional Relevance
5. CAFGs Collagens in BC and Novel Therapeutic Potential
6. Semi-CAFGs in BC and Novel Therapeutic Potential
7. CAFGs with Low SE (L-CAFGs) and Novel Therapeutic Potential in BC
8. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Bray, F.; Laversanne, M.; Sung, H.; Ferlay, J.; Siegel, R.L.; Soerjomataram, I.; Jemal, A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J. Clin. 2024, 74, 229–263. [Google Scholar] [CrossRef]
- Ignatiadis, M.; Sotiriou, C. Luminal breast cancer: From biology to treatment. Nat. Rev. Clin. Oncol. 2013, 10, 494–506. [Google Scholar] [CrossRef] [PubMed]
- Bianchini, G.; De Angelis, C.; Licata, L.; Gianni, L. Treatment landscape of triple-negative breast cancer—Expanded options, evolving needs. Nat. Rev. Clin. Oncol. 2022, 19, 91–113. [Google Scholar] [CrossRef] [PubMed]
- Yoon, J.; Oh, D.Y. HER2-targeted therapies beyond breast cancer—Un update. Nat. Rev. Clin. Oncol. 2024, 21, 675–700. [Google Scholar] [CrossRef]
- Perou, C.M. Comprehensive molecular portraits of human breast tumours. Nature 2012, 490, 61–70. [Google Scholar]
- Di Cosimo, S.; Baselga, J. Management of breast cancer with targeted agents: Importance of heterogeneity. Nat. Rev. Clin. Oncol. 2010, 7, 139–147. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, T.; Watanabe, M.; Yamashita, K. Potential therapeutic targets of TP53 gene in the context of its classically canonical functions and its latest non-canonical functions in human cancer. Oncotarget 2018, 9, 16234–16247. [Google Scholar] [CrossRef]
- Fong, P.C.; Boss, D.S.; Yap, T.A.; Tutt, A.; Wu, P.; Mergui-Roelvink, M.; Mortimer, P.; Swaisland, H.; Lau, A.; O’Connor, M.J.; et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med. 2009, 361, 123–134. [Google Scholar] [CrossRef]
- Friedman, G.; Levi-Galibov, O.; David, E.; Bornstein, C.; Giladi, A.; Dadiani, M.; Mayo, A.; Halperin, C.; Pevsner-Fischer, M.; Lavon, H.; et al. Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4(+) and PDPN(+) CAFs to clinical outcome. Nat. Cancer 2020, 1, 692–708. [Google Scholar] [CrossRef]
- Bartoschek, M.; Oskolkov, N.; Bocci, M.; Lövrot, J.; Larsson, C.; Sommarin, M.; Madsen, C.D.; Lindgren, D.; Pekar, G.; Karlsson, G.; et al. Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing. Nat. Commun. 2018, 9, 5150. [Google Scholar] [CrossRef]
- Lindstrom, L. Gene Signature Model Predicts Metastatic Onset Better than Standard Clinical Markers—Nested Case-Control Design Uniquely Enables Enrichment for Biologically Relevant Features. In Cancer Research; American Association Cancer Research: San Antonio, TX, USA, 2013; Volume 73. [Google Scholar]
- Curtis, C.; Shah, S.P.; Chin, S.F.; Turashvili, G.; Rueda, O.M.; Dunning, M.J.; Speed, D.; Lynch, A.G.; Samarajiwa, S.; Yuan, Y.; et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012, 486, 346–352. [Google Scholar] [CrossRef]
- Viré, E.; Curtis, C.; Davalos, V.; Git, A.; Robson, S.; Villanueva, A.; Vidal, A.; Barbieri, I.; Aparicio, S.; Esteller, M.; et al. The breast cancer oncogene EMSY represses transcription of antimetastatic microRNA miR-31. Mol. Cell 2014, 53, 806–818. [Google Scholar] [CrossRef] [PubMed]
- Pereira, B.; Chin, S.F.; Rueda, O.M.; Vollan, H.K.; Provenzano, E.; Bardwell, H.A.; Pugh, M.; Jones, L.; Russell, R.; Sammut, S.J.; et al. The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat. Commun. 2016, 7, 11479. [Google Scholar] [CrossRef] [PubMed]
- Farmer, P.; Bonnefoi, H.; Anderle, P.; Cameron, D.; Wirapati, P.; Becette, V.; André, S.; Piccart, M.; Campone, M.; Brain, E.; et al. A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat. Med. 2009, 15, 68–74. [Google Scholar] [CrossRef]
- Öhlund, D.; Handly-Santana, A.; Biffi, G.; Elyada, E.; Almeida, A.S.; Ponz-Sarvise, M.; Corbo, V.; Oni, T.E.; Hearn, S.A.; Lee, E.J.; et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J. Exp. Med. 2017, 214, 579–596. [Google Scholar] [CrossRef] [PubMed]
- Krishnamurty, A.T.; Shyer, J.A.; Thai, M.; Gandham, V.; Buechler, M.B.; Yang, Y.A.; Pradhan, R.N.; Wang, A.W.; Sanchez, P.L.; Qu, Y.; et al. LRRC15(+) myofibroblasts dictate the stromal setpoint to suppress tumour immunity. Nature 2022, 611, 148–154. [Google Scholar] [CrossRef]
- Biffi, G.; Oni, T.E.; Spielman, B.; Hao, Y.; Elyada, E.; Park, Y.; Preall, J.; Tuveson, D.A. IL1-Induced JAK/STAT Signaling Is Antagonized by TGFβ to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma. Cancer Discov. 2019, 9, 282–301. [Google Scholar] [CrossRef]
- Sahai, E.; Astsaturov, I.; Cukierman, E.; DeNardo, D.G.; Egeblad, M.; Evans, R.M.; Fearon, D.; Greten, F.R.; Hingorani, S.R.; Hunter, T.; et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer 2020, 20, 174–186. [Google Scholar] [CrossRef]
- Okuno, K.; Ikemura, K.; Okamoto, R.; Oki, K.; Watanabe, A.; Kuroda, Y.; Kidachi, M.; Fujino, S.; Nie, Y.; Higuchi, T.; et al. CAF-associated genes putatively representing distinct prognosis by in silico landscape of stromal components of colon cancer. PLoS ONE 2024, 19, e0299827. [Google Scholar] [CrossRef]
- Casey, T.; Bond, J.; Tighe, S.; Hunter, T.; Lintault, L.; Patel, O.; Eneman, J.; Crocker, A.; White, J.; Tessitore, J.; et al. Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer. Breast Cancer Res. Treat. 2009, 114, 47–62. [Google Scholar] [CrossRef]
- Nishida, N.; Nagahara, M.; Sato, T.; Mimori, K.; Sudo, T.; Tanaka, F.; Shibata, K.; Ishii, H.; Sugihara, K.; Doki, Y.; et al. Microarray analysis of colorectal cancer stromal tissue reveals upregulation of two oncogenic miRNA clusters. Clin Cancer Res. 2012, 18, 3054–3070. [Google Scholar] [CrossRef] [PubMed]
- Null, J.L.; Kim, D.J.; McCann, J.V.; Pramoonjago, P.; Fox, J.W.; Zeng, J.; Kumar, P.; Edatt, L.; Pecot, C.V.; Dudley, A.C. Periostin+ Stromal Cells Guide Lymphovascular Invasion by Cancer Cells. Cancer Res. 2023, 83, 2105–2122. [Google Scholar] [CrossRef] [PubMed]
- Madsen, C.D.; Pedersen, J.T.; Venning, F.A.; Singh, L.B.; Moeendarbary, E.; Charras, G.; Cox, T.R.; Sahai, E.; Erler, J.T. Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis. EMBO Rep. 2015, 16, 1394–1408. [Google Scholar] [CrossRef]
- Chaiwun, B.; Sukhamwang, N.; Trakultivakorn, H.; Saha, B.; Young, L.; Tsao-Wei, D.; Naritoku, W.Y.; Groshen, S.; Taylor, C.R.; Imam, S.A. GSTPi-positive tumour microenvironment-associated fibroblasts are significantly associated with GSTPi-negative cancer cells in paired cases of primary invasive breast cancer and axillary lymph node metastases. Br. J. Cancer 2011, 105, 1224–1229. [Google Scholar] [CrossRef] [PubMed]
- Al-Rakan, M.A.; Colak, D.; Hendrayani, S.F.; Al-Bakheet, A.; Al-Mohanna, F.H.; Kaya, N.; Al-Malik, O.; Aboussekhra, A. Breast stromal fibroblasts from histologically normal surgical margins are pro-carcinogenic. J. Pathol. 2013, 231, 457–465. [Google Scholar] [CrossRef]
- Ao, Z.; Shah, S.H.; Machlin, L.M.; Parajuli, R.; Miller, P.C.; Rawal, S.; Williams, A.J.; Cote, R.J.; Lippman, M.E.; Datar, R.H.; et al. Identification of Cancer-Associated Fibroblasts in Circulating Blood from Patients with Metastatic Breast Cancer. Cancer Res. 2015, 75, 4681–4687. [Google Scholar] [CrossRef]
- Ferrari, N.; Ranftl, R.; Chicherova, I.; Slaven, N.D.; Moeendarbary, E.; Farrugia, A.J.; Lam, M.; Semiannikova, M.; Westergaard, M.C.W.; Tchou, J.; et al. Dickkopf-3 links HSF1 and YAP/TAZ signalling to control aggressive behaviours in cancer-associated fibroblasts. Nat. Commun. 2019, 10, 130. [Google Scholar] [CrossRef]
- Primac, I.; Maquoi, E.; Blacher, S.; Heljasvaara, R.; Van Deun, J.; Smeland, H.Y.; Canale, A.; Louis, T.; Stuhr, L.; Sounni, N.E.; et al. Stromal integrin α11 regulates PDGFR-β signaling and promotes breast cancer progression. J. Clin. Investig. 2019, 129, 4609–4628. [Google Scholar] [CrossRef]
- Licaj, M.; Mhaidly, R.; Kieffer, Y.; Croizer, H.; Bonneau, C.; Meng, A.; Djerroudi, L.; Mujangi-Ebeka, K.; Hocine, H.R.; Bourachot, B.; et al. Residual ANTXR1+ myofibroblasts after chemotherapy inhibit anti-tumor immunity via YAP1 signaling pathway. Nat. Commun. 2024, 15, 1312. [Google Scholar] [CrossRef]
- Kieffer, Y.; Hocine, H.R.; Gentric, G.; Pelon, F.; Bernard, C.; Bourachot, B.; Lameiras, S.; Albergante, L.; Bonneau, C.; Guyard, A.; et al. Single-Cell Analysis Reveals Fibroblast Clusters Linked to Immunotherapy Resistance in Cancer. Cancer Discov. 2020, 10, 1330–1351. [Google Scholar] [CrossRef]
- Bauer, M.; Su, G.; Casper, C.; He, R.; Rehrauer, W.; Friedl, A. Heterogeneity of gene expression in stromal fibroblasts of human breast carcinomas and normal breast. Oncogene 2010, 29, 1732–1740. [Google Scholar] [CrossRef]
- Nagaraja, A.S.; Dood, R.L.; Armaiz-Pena, G.; Kang, Y.; Wu, S.Y.; Allen, J.K.; Jennings, N.B.; Mangala, L.S.; Pradeep, S.; Lyons, Y.; et al. Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens. JCI Insight 2017, 2, e93076. [Google Scholar] [CrossRef] [PubMed]
- Cohen, N.; Mundhe, D.; Deasy, S.K.; Adler, O.; Ershaid, N.; Shami, T.; Levi-Galibov, O.; Wassermann, R.; Scherz-Shouval, R.; Erez, N.; et al. Breast Cancer-Secreted Factors Promote Lung Metastasis by Signaling Systemically to Induce a Fibrotic Premetastatic Niche. Cancer Res. 2023, 83, 3354–3367. [Google Scholar] [CrossRef] [PubMed]
- Tsuyada, A.; Chow, A.; Wu, J.; Somlo, G.; Chu, P.; Loera, S.; Luu, T.; Li, A.X.; Wu, X.; Ye, W.; et al. CCL2 mediates cross-talk between cancer cells and stromal fibroblasts that regulates breast cancer stem cells. Cancer Res. 2012, 72, 2768–2779. [Google Scholar] [CrossRef] [PubMed]
- Papanicolaou, M.; Parker, A.L.; Yam, M.; Filipe, E.C.; Wu, S.Z.; Chitty, J.L.; Wyllie, K.; Tran, E.; Mok, E.; Nadalini, A.; et al. Temporal profiling of the breast tumour microenvironment reveals collagen XII as a driver of metastasis. Nat. Commun. 2022, 13, 4587. [Google Scholar] [CrossRef] [PubMed]
- Bochet, L.; Lehuédé, C.; Dauvillier, S.; Wang, Y.Y.; Dirat, B.; Laurent, V.; Dray, C.; Guiet, R.; Maridonneau-Parini, I.; Le Gonidec, S.; et al. Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer. Cancer Res. 2013, 73, 5657–5668. [Google Scholar] [CrossRef]
- Jungwirth, U.; van Weverwijk, A.; Evans, R.J.; Jenkins, L.; Vicente, D.; Alexander, J.; Gao, Q.; Haider, S.; Iravani, M.; Isacke, C.M. Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis. Nat. Commun. 2021, 12, 3516. [Google Scholar] [CrossRef]
- Kay, E.J.; Paterson, K.; Riera-Domingo, C.; Sumpton, D.; Däbritz, J.H.M.; Tardito, S.; Boldrini, C.; Hernandez-Fernaud, J.R.; Athineos, D.; Dhayade, S.; et al. Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. Nat. Metab. 2022, 4, 693–710. [Google Scholar] [CrossRef]
- Shimoda, M.; Principe, S.; Jackson, H.W.; Luga, V.; Fang, H.; Molyneux, S.D.; Shao, Y.W.; Aiken, A.; Waterhouse, P.D.; Karamboulas, C.; et al. Loss of the Timp gene family is sufficient for the acquisition of the CAF-like cell state. Nat. Cell Biol. 2014, 16, 889–901. [Google Scholar] [CrossRef]
- Liu, C.; Zhang, Y.; Lim, S.; Hosaka, K.; Yang, Y.; Pavlova, T.; Alkasalias, T.; Hartman, J.; Jensen, L.; Xing, X.; et al. A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis. Clin. Cancer Res. 2017, 23, 4769–4779. [Google Scholar] [CrossRef]
- Kojima, Y.; Acar, A.; Eaton, E.N.; Mellody, K.T.; Scheel, C.; Ben-Porath, I.; Onder, T.T.; Wang, Z.C.; Richardson, A.L.; Weinberg, R.A.; et al. Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc. Natl. Acad. Sci. USA 2010, 107, 20009–20014. [Google Scholar] [CrossRef] [PubMed]
- Yu, Y.; Xiao, C.H.; Tan, L.D.; Wang, Q.S.; Li, X.Q.; Feng, Y.M. Cancer-associated fibroblasts induce epithelial-mesenchymal transition of breast cancer cells through paracrine TGF-β signalling. Br. J. Cancer 2014, 110, 724–732. [Google Scholar] [CrossRef]
- Scherz-Shouval, R.; Santagata, S.; Mendillo, M.L.; Sholl, L.M.; Ben-Aharon, I.; Beck, A.H.; Dias-Santagata, D.; Koeva, M.; Stemmer, S.M.; Whitesell, L.; et al. The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy. Cell 2014, 158, 564–578. [Google Scholar] [CrossRef]
- Cook, K.L.; Metheny-Barlow, L.J.; Tallant, E.A.; Gallagher, P.E. Angiotensin-(1-7) reduces fibrosis in orthotopic breast tumors. Cancer Res. 2010, 70, 8319–8328. [Google Scholar] [CrossRef]
- Chauhan, V.P.; Chen, I.X.; Tong, R.; Ng, M.R.; Martin, J.D.; Naxerova, K.; Wu, M.W.; Huang, P.; Boucher, Y.; Kohane, D.S.; et al. Reprogramming the microenvironment with tumor-selective angiotensin blockers enhances cancer immunotherapy. Proc. Natl. Acad. Sci. USA 2019, 116, 10674–10680. [Google Scholar] [CrossRef]
- Zhang, Q.; Zhou, N.; Wang, W.; Zhou, S. A Novel Autocrine CXCL14/ACKR2 Axis: The Achilles’ Heel of Cancer Metastasis? Clin Cancer Res 2019, 25, 3476–3478. [Google Scholar] [CrossRef]
- Stanisavljevic, J.; Loubat-Casanovas, J.; Herrera, M.; Luque, T.; Peña, R.; Lluch, A.; Albanell, J.; Bonilla, F.; Rovira, A.; Peña, C.; et al. Snail1-expressing fibroblasts in the tumor microenvironment display mechanical properties that support metastasis. Cancer Res. 2015, 75, 284–295. [Google Scholar] [CrossRef] [PubMed]
- Alba-Castellón, L.; Olivera-Salguero, R.; Mestre-Farrera, A.; Peña, R.; Herrera, M.; Bonilla, F.; Casal, J.I.; Baulida, J.; Peña, C.; García de Herreros, A. Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis. Cancer Res. 2016, 76, 6205–6217. [Google Scholar] [CrossRef] [PubMed]
- Zeng, W.; Xiong, L.; Wu, W.; Li, S.; Liu, J.; Yang, L.; Lao, L.; Huang, P.; Zhang, M.; Chen, H.; et al. CCL18 signaling from tumor-associated macrophages activates fibroblasts to adopt a chemoresistance-inducing phenotype. Oncogene 2023, 42, 224–237. [Google Scholar] [CrossRef]
- Weber, C.E.; Kothari, A.N.; Wai, P.Y.; Li, N.Y.; Driver, J.; Zapf, M.A.; Franzen, C.A.; Gupta, G.N.; Osipo, C.; Zlobin, A.; et al. Osteopontin mediates an MZF1-TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene 2015, 34, 4821–4833. [Google Scholar] [CrossRef]
- Sharon, Y.; Raz, Y.; Cohen, N.; Ben-Shmuel, A.; Schwartz, H.; Geiger, T.; Geiger, T.; Erez, N. Tumor-derived osteopontin reprograms normal mammary fibroblasts to promote inflammation and tumor growth in breast cancer. Cancer Res. 2015, 75, 963–973. [Google Scholar] [CrossRef]
- Avgustinova, A.; Iravani, M.; Robertson, D.; Fearns, A.; Gao, Q.; Klingbeil, P.; Hanby, A.M.; Speirs, V.; Sahai, E.; Calvo, F.; et al. Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness. Nat. Commun. 2016, 7, 10305. [Google Scholar] [CrossRef]
- Li, Q.; Yuan, H.; Zhao, G.; Zhang, J.; Li, S.; Gong, D.; Feng, T.; Kou, Q.; Wang, Q.; Wang, G.; et al. ZNF32 prevents the activation of cancer-associated fibroblasts through negative regulation of TGFB1 transcription in breast cancer. FASEB J. 2023, 37, e22837. [Google Scholar] [CrossRef] [PubMed]
- Pelon, F.; Bourachot, B.; Kieffer, Y.; Magagna, I.; Mermet-Meillon, F.; Bonnet, I.; Costa, A.; Givel, A.M.; Attieh, Y.; Barbazan, J.; et al. Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms. Nat. Commun. 2020, 11, 404. [Google Scholar] [CrossRef] [PubMed]
- Timperi, E.; Gueguen, P.; Molgora, M.; Magagna, I.; Kieffer, Y.; Lopez-Lastra, S.; Sirven, P.; Baudrin, L.G.; Baulande, S.; Nicolas, A.; et al. Lipid-Associated Macrophages Are Induced by Cancer-Associated Fibroblasts and Mediate Immune Suppression in Breast Cancer. Cancer Res. 2022, 82, 3291–3306. [Google Scholar] [CrossRef] [PubMed]
- Reid, S.E.; Pantaleo, J.; Bolivar, P.; Bocci, M.; Sjölund, J.; Morsing, M.; Cordero, E.; Larsson, S.; Malmberg, M.; Seashore-Ludlow, B.; et al. Cancer-associated fibroblasts rewire the estrogen receptor response in luminal breast cancer, enabling estrogen independence. Oncogene 2024, 43, 1113–1126. [Google Scholar] [CrossRef] [PubMed]
- Mayer, S.; Milo, T.; Isaacson, A.; Halperin, C.; Miyara, S.; Stein, Y.; Lior, C.; Pevsner-Fischer, M.; Tzahor, E.; Mayo, A.; et al. The tumor microenvironment shows a hierarchy of cell-cell interactions dominated by fibroblasts. Nat. Commun. 2023, 14, 5810. [Google Scholar] [CrossRef]
- De Vincenzo, A.; Belli, S.; Franco, P.; Telesca, M.; Iaccarino, I.; Botti, G.; Carriero, M.V.; Ranson, M.; Stoppelli, M.P. Paracrine recruitment and activation of fibroblasts by c-Myc expressing breast epithelial cells through the IGFs/IGF-1R axis. Int. J. Cancer 2019, 145, 2827–2839. [Google Scholar] [CrossRef]
- Gui, Y.; Aguilar-Mahecha, A.; Krzemien, U.; Hosein, A.; Buchanan, M.; Lafleur, J.; Pollak, M.; Ferrario, C.; Basik, M. Metastatic Breast Carcinoma-Associated Fibroblasts Have Enhanced Protumorigenic Properties Related to Increased IGF2 Expression. Clin. Cancer Res. 2019, 25, 7229–7242. [Google Scholar] [CrossRef]
- Butti, R.; Nimma, R.; Kundu, G.; Bulbule, A.; Kumar, T.V.S.; Gunasekaran, V.P.; Tomar, D.; Kumar, D.; Mane, A.; Gill, S.S.; et al. Tumor-derived osteopontin drives the resident fibroblast to myofibroblast differentiation through Twist1 to promote breast cancer progression. Oncogene 2021, 40, 2002–2017. [Google Scholar] [CrossRef]
- Yamamura, Y.; Asai, N.; Enomoto, A.; Kato, T.; Mii, S.; Kondo, Y.; Ushida, K.; Niimi, K.; Tsunoda, N.; Nagino, M.; et al. Akt-Girdin signaling in cancer-associated fibroblasts contributes to tumor progression. Cancer Res. 2015, 75, 813–823. [Google Scholar] [CrossRef] [PubMed]
- Su, S.; Chen, J.; Yao, H.; Liu, J.; Yu, S.; Lao, L.; Wang, M.; Luo, M.; Xing, Y.; Chen, F.; et al. CD10(+)GPR77(+) Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness. Cell 2018, 172, 841–856. [Google Scholar] [CrossRef] [PubMed]
- Elwakeel, E.; Brüggemann, M.; Wagih, J.; Lityagina, O.; Elewa, M.A.F.; Han, Y.; Frömel, T.; Popp, R.; Nicolas, A.M.; Schreiber, Y.; et al. Disruption of Prostaglandin E2 Signaling in Cancer-Associated Fibroblasts Limits Mammary Carcinoma Growth but Promotes Metastasis. Cancer Res. 2022, 82, 1380–1395. [Google Scholar] [CrossRef]
- Boyle, S.T.; Poltavets, V.; Kular, J.; Pyne, N.T.; Sandow, J.J.; Lewis, A.C.; Murphy, K.J.; Kolesnikoff, N.; Moretti, P.A.B.; Tea, M.N.; et al. ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism. Nat. Cell Biol. 2020, 22, 882–895. [Google Scholar] [CrossRef]
- Thorlacius-Ussing, J.; Jensen, C.; Nissen, N.I.; Cox, T.R.; Kalluri, R.; Karsdal, M.; Willumsen, N. The collagen landscape in cancer: Profiling collagens in tumors and in circulation reveals novel markers of cancer-associated fibroblast subtypes. J. Pathol. 2024, 262, 22–36. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 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
Naito, K.; Sangai, T.; Yamashita, K. CAF-Associated Genes in Breast Cancer for Novel Therapeutic Strategies. Biomedicines 2024, 12, 1964. https://doi.org/10.3390/biomedicines12091964
Naito K, Sangai T, Yamashita K. CAF-Associated Genes in Breast Cancer for Novel Therapeutic Strategies. Biomedicines. 2024; 12(9):1964. https://doi.org/10.3390/biomedicines12091964
Chicago/Turabian StyleNaito, Kanako, Takafumi Sangai, and Keishi Yamashita. 2024. "CAF-Associated Genes in Breast Cancer for Novel Therapeutic Strategies" Biomedicines 12, no. 9: 1964. https://doi.org/10.3390/biomedicines12091964