Multi-Functional Regulation by YAP/TAZ Signaling Networks in Tumor Progression and Metastasis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Structure and Regulation of YAP and TAZ
2.1. YAP and TAZ Structural Domains and Interacting Proteins
2.2. Hippo-Pathway-Mediated Regulation of YAP/TAZ Signaling
2.3. Tyrosine Kinases, GPCRs, and Adhesion Receptors Regulate YAP/TAZ Signaling through Hippo-Dependent and Hippo-Independent Pathways
3. YAP and TAZ Promote Tumor Progression and Metastasis through Dysregulation of Diverse Cellular Processes
3.1. Role of YAP/TAZ in the Regulation of Reversible EMT, Migration, and Invasion
3.2. Role of YAP/TAZ in the Regulation of Tumor–Endothelial Cell Interactions: Entry and Exit from the Vasculature and Intravascular Motility
3.3. Role of YAP/TAZ in Seeding and Colonization
3.4. YAP/TAZ Promote Therapy Resistance and Acquisition of Cancer Stem Cell Phenotypes, Leading to Enhanced Metastasis
4. Transcriptional and Epigenetic Targets of YAP and TAZ in Cancer Cells
5. Therapeutic Strategies for Targeting YAP/TAZ Signaling in Metastatic and Therapy-Resistant Tumors
5.1. Targeting YAP/TAZ and TEAD Expression and Interaction
5.2. Therapies Targeting YAP/TAZ Regulatory Factors
6. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ABL1 (c-ABL) and ABL2 (Arg) | Abelson Murine Leukemia Viral Oncogene Homologs 1 and 2 |
AMOT | Angiomotin |
ARHGAP29 | Rho GTPase-Activating Protein 29 |
BBB | Blood–Brain Barrier |
BET | Bromodomain and Extraterminal Domain |
BRD4 | Bromodomain-Containing Protein 4 |
CAMK2 | Calcium/Calmodulin-Dependent Kinase 2 |
CC | Coiled Coil Domain |
COX-2 | Cyclooxygenase 2 |
CSC | Cancer Stem Cells |
CTGF | Connective Tissue Growth Factor |
DCC | Disseminated Cancer Cells |
EHE | Epithelioid HemangioEndothelioma |
EMT | Epithelial–Mesenchymal Transition |
ERK | Extracellular Signal-Regulated Kinases |
FAK | Focal Adhesion Kinase |
GBM | Glioblastoma |
GGPP | Geranylgeranyl pyrophosphate |
GIT1 | GPCR-kinase-Interacting Protein 1 |
GPCRs | G-Protein-Coupled Receptors |
HMG-CoA | 3-hydroxy-3-methylglutaryl coenzyme A |
hnRNP | Heterogeneous Nuclear Ribonucleoproteins |
HNSCC | Head and Nek Cancer Squamous Cell Carcinoma |
L1CAM | Cell Adhesion Molecule 1 |
LATS 1/2 | Large Tumor Suppressor Homologs 1 and 2 |
MET | Mesenchymal–Epithelial Transition |
MOB 1A/B | MOB Kinase Activator 1A and B |
MSLN | Mesothelin |
MST 1/2 | Mammalian Sterile 20-Like Kinase 1 and 2 |
NDR1/2 | Nuclear Dbf2-Related Kinase 1 and 2 |
NES | Nuclear Export Signal |
NHERF | Na+/H+ Exchange Regulatory Cofactor |
NLS | Nuclear Localization Signal |
NSAID | Non-Steroidal Anti-Inflammatory Drug |
PAX3 | Paired Box Gene 3 |
PDZ BD | PDZ Binding Domain |
PI3K | Phosphatidylinositol 4,5-bisphosphate 3-kinase |
RASSF1-6 | Ras Association Domain Family Members 1-6 |
RASSF1A | Ras Association Domain Family Protein 1 Isoform A |
ROCK | Rho-Kinase Pathway |
SAV1 | Salvador |
SH BD | Src Homology Binding Domain |
TAD | Transactivation Domain |
TAZ | Transcriptional Co-Activator with PDZ Binding Motif |
TBX5 | T-box Transcription Factor 5 |
TEAD BD | TEAD Binding Domain |
TGF-β | Transforming Growth Factor-β |
TME | Tumor Microenvironment |
TSP1 | Thrombospondin 1 |
YAP | YES-Associated Protein |
ZO 1/2 | Zona Occludens 1 and 2 |
References
- Piccolo, S.; Panciera, T.; Contessotto, P.; Cordenonsi, M. YAP/TAZ as master regulators in cancer: Modulation, function and therapeutic approaches. Nat. Cancer 2023, 4, 9–26. [Google Scholar] [CrossRef]
- Warren, J.S.A.; Xiao, Y.; Lamar, J.M. YAP/TAZ Activation as a Target for Treating Metastatic Cancer. Cancers 2018, 10, 115. [Google Scholar] [CrossRef] [PubMed]
- Plouffe, S.W.; Lin, K.C.; Moore, J.L., 3rd; Tan, F.E.; Ma, S.; Ye, Z.; Qiu, Y.; Ren, B.; Guan, K.L. The Hippo pathway effector proteins YAP and TAZ have both distinct and overlapping functions in the cell. J. Biol. Chem. 2018, 293, 11230–11240. [Google Scholar] [CrossRef] [PubMed]
- Shreberk-Shaked, M.; Dassa, B.; Sinha, S.; Di Agostino, S.; Azuri, I.; Mukherjee, S.; Aylon, Y.; Blandino, G.; Ruppin, E.; Oren, M. A Division of Labor between YAP and TAZ in Non-Small Cell Lung Cancer. Cancer Res. 2020, 80, 4145–4157. [Google Scholar] [CrossRef]
- Reggiani, F.; Gobbi, G.; Ciarrocchi, A.; Sancisi, V. YAP and TAZ Are Not Identical Twins. Trends Biochem. Sci. 2021, 46, 154–168. [Google Scholar] [CrossRef]
- Sudol, M. Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product. Oncogene 1994, 9, 2145–2152. [Google Scholar] [PubMed]
- Kanai, F.; Marignani, P.A.; Sarbassova, D.; Yagi, R.; Hall, R.A.; Donowitz, M.; Hisaminato, A.; Fujiwara, T.; Ito, Y.; Cantley, L.C.; et al. TAZ: A novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins. EMBO J. 2000, 19, 6778–6791. [Google Scholar] [CrossRef]
- Varelas, X. The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development 2014, 141, 1614–1626. [Google Scholar] [CrossRef]
- Yu, F.X.; Zhao, B.; Guan, K.L. Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. Cell 2015, 163, 811–828. [Google Scholar] [CrossRef]
- Hsu, S.C.; Lin, C.Y.; Lin, Y.Y.; Collins, C.C.; Chen, C.L.; Kung, H.J. TEAD4 as an Oncogene and a Mitochondrial Modulator. Front. Cell Dev. Biol. 2022, 10, 890419. [Google Scholar] [CrossRef]
- Chang, L.; Azzolin, L.; Di Biagio, D.; Zanconato, F.; Battilana, G.; Lucon Xiccato, R.; Aragona, M.; Giulitti, S.; Panciera, T.; Gandin, A.; et al. The SWI/SNF complex is a mechanoregulated inhibitor of YAP and TAZ. Nature 2018, 563, 265–269. [Google Scholar] [CrossRef]
- Karaman, R.; Halder, G. Cell Junctions in Hippo Signaling. Cold Spring Harb. Perspect. Biol. 2018, 10, a028753. [Google Scholar] [CrossRef] [PubMed]
- El Ouarrat, D.; Isaac, R.; Lee, Y.S.; Oh, D.Y.; Wollam, J.; Lackey, D.; Riopel, M.; Bandyopadhyay, G.; Seo, J.B.; Sampath-Kumar, R.; et al. TAZ Is a Negative Regulator of PPARgamma Activity in Adipocytes and TAZ Deletion Improves Insulin Sensitivity and Glucose Tolerance. Cell Metab. 2020, 31, 162–173 e165. [Google Scholar] [CrossRef]
- Zhao, B.; Wei, X.; Li, W.; Udan, R.S.; Yang, Q.; Kim, J.; Xie, J.; Ikenoue, T.; Yu, J.; Li, L.; et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes. Dev. 2007, 21, 2747–2761. [Google Scholar] [CrossRef] [PubMed]
- Holt, L.J. Regulatory modules: Coupling protein stability to phopshoregulation during cell division. FEBS Lett. 2012, 586, 2773–2777. [Google Scholar] [CrossRef] [PubMed]
- Kofler, M.; Speight, P.; Little, D.; Di Ciano-Oliveira, C.; Szaszi, K.; Kapus, A. Mediated nuclear import and export of TAZ and the underlying molecular requirements. Nat. Commun. 2018, 9, 4966. [Google Scholar] [CrossRef]
- Zheng, Y.; Pan, D. The Hippo Signaling Pathway in Development and Disease. Dev. Cell 2019, 50, 264–282. [Google Scholar] [CrossRef]
- Huang, J.; Wu, S.; Barrera, J.; Matthews, K.; Pan, D. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. Cell 2005, 122, 421–434. [Google Scholar] [CrossRef]
- Harvey, K.F.; Pfleger, C.M.; Hariharan, I.K. The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell 2003, 114, 457–467. [Google Scholar] [CrossRef]
- Tapon, N.; Harvey, K.F.; Bell, D.W.; Wahrer, D.C.; Schiripo, T.A.; Haber, D.; Hariharan, I.K. salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell 2002, 110, 467–478. [Google Scholar] [CrossRef]
- Zhang, J.; Smolen, G.A.; Haber, D.A. Negative regulation of YAP by LATS1 underscores evolutionary conservation of the Drosophila Hippo pathway. Cancer Res. 2008, 68, 2789–2794. [Google Scholar] [CrossRef]
- Poon, C.L.; Lin, J.I.; Zhang, X.; Harvey, K.F. The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway. Dev. Cell 2011, 21, 896–906. [Google Scholar] [CrossRef] [PubMed]
- Boggiano, J.C.; Vanderzalm, P.J.; Fehon, R.G. Tao-1 phosphorylates Hippo/MST kinases to regulate the Hippo-Salvador-Warts tumor suppressor pathway. Dev. Cell 2011, 21, 888–895. [Google Scholar] [CrossRef]
- Zhang, L.; Tang, F.; Terracciano, L.; Hynx, D.; Kohler, R.; Bichet, S.; Hess, D.; Cron, P.; Hemmings, B.A.; Hergovich, A.; et al. NDR functions as a physiological YAP1 kinase in the intestinal epithelium. Curr. Biol. 2015, 25, 296–305. [Google Scholar] [CrossRef] [PubMed]
- Avruch, J.; Zhou, D.; Fitamant, J.; Bardeesy, N.; Mou, F.; Barrufet, L.R. Protein kinases of the Hippo pathway: Regulation and substrates. Semin. Cell Dev. Biol. 2012, 23, 770–784. [Google Scholar] [CrossRef] [PubMed]
- Martin, D.; Degese, M.S.; Vitale-Cross, L.; Iglesias-Bartolome, R.; Valera, J.L.C.; Wang, Z.; Feng, X.; Yeerna, H.; Vadmal, V.; Moroishi, T.; et al. Assembly and activation of the Hippo signalome by FAT1 tumor suppressor. Nat. Commun. 2018, 9, 2372. [Google Scholar] [CrossRef]
- Morris, L.G.; Kaufman, A.M.; Gong, Y.; Ramaswami, D.; Walsh, L.A.; Turcan, S.; Eng, S.; Kannan, K.; Zou, Y.; Peng, L.; et al. Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation. Nat. Genet. 2013, 45, 253–261. [Google Scholar] [CrossRef]
- Lamar, J.M.; Stern, P.; Liu, H.; Schindler, J.W.; Jiang, Z.G.; Hynes, R.O. The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain. Proc. Natl. Acad. Sci. USA 2012, 109, E2441–E2450. [Google Scholar] [CrossRef]
- Matallanas, D.; Romano, D.; Yee, K.; Meissl, K.; Kucerova, L.; Piazzolla, D.; Baccarini, M.; Vass, J.K.; Kolch, W.; O’Neill, E. RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. Mol. Cell 2007, 27, 962–975. [Google Scholar] [CrossRef]
- Grawenda, A.M.; O’Neill, E. Clinical utility of RASSF1A methylation in human malignancies. Br. J. Cancer 2015, 113, 372–381. [Google Scholar] [CrossRef]
- Malpeli, G.; Innamorati, G.; Decimo, I.; Bencivenga, M.; Nwabo Kamdje, A.H.; Perris, R.; Bassi, C. Methylation Dynamics of RASSF1A and Its Impact on Cancer. Cancers 2019, 11, 959. [Google Scholar] [CrossRef] [PubMed]
- Pefani, D.E.; Pankova, D.; Abraham, A.G.; Grawenda, A.M.; Vlahov, N.; Scrace, S.; O’Neill, E. TGF-beta Targets the Hippo Pathway Scaffold RASSF1A to Facilitate YAP/SMAD2 Nuclear Translocation. Mol. Cell 2016, 63, 156–166. [Google Scholar] [CrossRef]
- Romano, D.; Nguyen, L.K.; Matallanas, D.; Halasz, M.; Doherty, C.; Kholodenko, B.N.; Kolch, W. Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling. Nat. Cell Biol. 2014, 16, 673–684. [Google Scholar] [CrossRef] [PubMed]
- O’Neill, E.; Rushworth, L.; Baccarini, M.; Kolch, W. Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. Science 2004, 306, 2267–2270. [Google Scholar] [CrossRef] [PubMed]
- Vlahov, N.; Scrace, S.; Soto, M.S.; Grawenda, A.M.; Bradley, L.; Pankova, D.; Papaspyropoulos, A.; Yee, K.S.; Buffa, F.; Goding, C.R.; et al. Alternate RASSF1 Transcripts Control SRC Activity, E-Cadherin Contacts, and YAP-Mediated Invasion. Curr. Biol. 2015, 25, 3019–3034. [Google Scholar] [CrossRef] [PubMed]
- Papaspyropoulos, A.; Bradley, L.; Thapa, A.; Leung, C.Y.; Toskas, K.; Koennig, D.; Pefani, D.E.; Raso, C.; Grou, C.; Hamilton, G.; et al. RASSF1A uncouples Wnt from Hippo signalling and promotes YAP mediated differentiation via p73. Nat. Commun. 2018, 9, 424. [Google Scholar] [CrossRef] [PubMed]
- Chen, J.; Wu, L.; Xu, H.; Cheng, S. 5-Aza-CdR Regulates RASSF1A By Inhibiting DNMT1 To Affect Colon Cancer Cell Proliferation, Migration And Apoptosis. Cancer Manag. Res. 2019, 11, 9517–9528. [Google Scholar] [CrossRef]
- Mengxi, D.; Qian, W.; Nan, W.; Xiaoguang, X.; Shijun, L. Effect of DNA methylation inhibitor on RASSF1A genes expression in non-small cell lung cancer cell line A549 and A549DDP. Cancer Cell Int. 2013, 13, 91. [Google Scholar] [CrossRef] [PubMed]
- Gnyszka, A.; Jastrzebski, Z.; Flis, S. DNA methyltransferase inhibitors and their emerging role in epigenetic therapy of cancer. Anticancer. Res. 2013, 33, 2989–2996. [Google Scholar]
- Pocaterra, A.; Romani, P.; Dupont, S. YAP/TAZ functions and their regulation at a glance. J. Cell Sci. 2020, 133, jcs230425. [Google Scholar] [CrossRef]
- Heng, B.C.; Zhang, X.; Aubel, D.; Bai, Y.; Li, X.; Wei, Y.; Fussenegger, M.; Deng, X. An overview of signaling pathways regulating YAP/TAZ activity. Cell Mol. Life Sci. 2021, 78, 497–512. [Google Scholar] [CrossRef] [PubMed]
- Rosenbluh, J.; Nijhawan, D.; Cox, A.G.; Li, X.; Neal, J.T.; Schafer, E.J.; Zack, T.I.; Wang, X.; Tsherniak, A.; Schinzel, A.C.; et al. beta-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis. Cell 2012, 151, 1457–1473. [Google Scholar] [CrossRef] [PubMed]
- Guegan, J.P.; Lapouge, M.; Voisin, L.; Saba-El-Leil, M.K.; Tanguay, P.L.; Levesque, K.; Bregeon, J.; Mes-Masson, A.M.; Lamarre, D.; Haibe-Kains, B.; et al. Signaling by the tyrosine kinase Yes promotes liver cancer development. Sci. Signal 2022, 15, eabj4743. [Google Scholar] [CrossRef]
- Li, P.; Silvis, M.R.; Honaker, Y.; Lien, W.H.; Arron, S.T.; Vasioukhin, V. alphaE-catenin inhibits a Src-YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway. Genes. Dev. 2016, 30, 798–811. [Google Scholar] [CrossRef] [PubMed]
- Si, Y.; Ji, X.; Cao, X.; Dai, X.; Xu, L.; Zhao, H.; Guo, X.; Yan, H.; Zhang, H.; Zhu, C.; et al. Src Inhibits the Hippo Tumor Suppressor Pathway through Tyrosine Phosphorylation of Lats1. Cancer Res. 2017, 77, 4868–4880. [Google Scholar] [CrossRef]
- Kim, N.G.; Gumbiner, B.M. Adhesion to fibronectin regulates Hippo signaling via the FAK-Src-PI3K pathway. J. Cell Biol. 2015, 210, 503–515. [Google Scholar] [CrossRef]
- Lamar, J.M.; Xiao, Y.; Norton, E.; Jiang, Z.G.; Gerhard, G.M.; Kooner, S.; Warren, J.S.A.; Hynes, R.O. SRC tyrosine kinase activates the YAP/TAZ axis and thereby drives tumor growth and metastasis. J. Biol. Chem. 2019, 294, 2302–2317. [Google Scholar] [CrossRef] [PubMed]
- Shanzer, M.; Adler, J.; Ricardo-Lax, I.; Reuven, N.; Shaul, Y. The nonreceptor tyrosine kinase c-Src attenuates SCF(beta-TrCP) E3-ligase activity abrogating Taz proteasomal degradation. Proc. Natl. Acad. Sci. USA 2017, 114, 1678–1683. [Google Scholar] [CrossRef]
- Levy, D.; Adamovich, Y.; Reuven, N.; Shaul, Y. Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage. Mol. Cell 2008, 29, 350–361. [Google Scholar] [CrossRef] [PubMed]
- Jang, E.J.; Jeong, H.; Han, K.H.; Kwon, H.M.; Hong, J.H.; Hwang, E.S. TAZ suppresses NFAT5 activity through tyrosine phosphorylation. Mol. Cell Biol. 2012, 32, 4925–4932. [Google Scholar] [CrossRef] [PubMed]
- Gu, J.J.; Rouse, C.; Xu, X.; Wang, J.; Onaitis, M.W.; Pendergast, A.M. Inactivation of ABL kinases suppresses non-small cell lung cancer metastasis. JCI Insight 2016, 1, e89647. [Google Scholar] [CrossRef] [PubMed]
- Hoj, J.P.; Mayro, B.; Pendergast, A.M. A TAZ-AXL-ABL2 Feed-Forward Signaling Axis Promotes Lung Adenocarcinoma Brain Metastasis. Cell Rep. 2019, 29, 3421–3434 e3428. [Google Scholar] [CrossRef] [PubMed]
- Pastushenko, I.; Mauri, F.; Song, Y.; de Cock, F.; Meeusen, B.; Swedlund, B.; Impens, F.; Van Haver, D.; Opitz, M.; Thery, M.; et al. Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis. Nature 2021, 589, 448–455. [Google Scholar] [CrossRef] [PubMed]
- Yu, F.X.; Zhao, B.; Panupinthu, N.; Jewell, J.L.; Lian, I.; Wang, L.H.; Zhao, J.; Yuan, H.; Tumaneng, K.; Li, H.; et al. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 2012, 150, 780–791. [Google Scholar] [CrossRef] [PubMed]
- Feng, X.; Degese, M.S.; Iglesias-Bartolome, R.; Vaque, J.P.; Molinolo, A.A.; Rodrigues, M.; Zaidi, M.R.; Ksander, B.R.; Merlino, G.; Sodhi, A.; et al. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. Cancer Cell 2014, 25, 831–845. [Google Scholar] [CrossRef] [PubMed]
- Yu, F.X.; Luo, J.; Mo, J.S.; Liu, G.; Kim, Y.C.; Meng, Z.; Zhao, L.; Peyman, G.; Ouyang, H.; Jiang, W.; et al. Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell 2014, 25, 822–830. [Google Scholar] [CrossRef]
- Dupont, S.; Morsut, L.; Aragona, M.; Enzo, E.; Giulitti, S.; Cordenonsi, M.; Zanconato, F.; Le Digabel, J.; Forcato, M.; Bicciato, S.; et al. Role of YAP/TAZ in mechanotransduction. Nature 2011, 474, 179–183. [Google Scholar] [CrossRef]
- Xu, Z.; Orkwis, J.A.; Harris, G.M. Cell Shape and Matrix Stiffness Impact Schwann Cell Plasticity via YAP/TAZ and Rho GTPases. Int. J. Mol. Sci. 2021, 22, 4821. [Google Scholar] [CrossRef]
- Novev, J.K.; Heltberg, M.L.; Jensen, M.H.; Doostmohammadi, A. Spatiotemporal model of cellular mechanotransduction via Rho and YAP. Integr. Biol. 2021, 13, 197–209. [Google Scholar] [CrossRef]
- Feng, X.; Arang, N.; Rigiracciolo, D.C.; Lee, J.S.; Yeerna, H.; Wang, Z.; Lubrano, S.; Kishore, A.; Pachter, J.A.; Konig, G.M.; et al. A Platform of Synthetic Lethal Gene Interaction Networks Reveals that the GNAQ Uveal Melanoma Oncogene Controls the Hippo Pathway through FAK. Cancer Cell 2019, 35, 457–472 e455. [Google Scholar] [CrossRef]
- Sorrentino, G.; Ruggeri, N.; Specchia, V.; Cordenonsi, M.; Mano, M.; Dupont, S.; Manfrin, A.; Ingallina, E.; Sommaggio, R.; Piazza, S.; et al. Metabolic control of YAP and TAZ by the mevalonate pathway. Nat. Cell Biol. 2014, 16, 357–366. [Google Scholar] [CrossRef] [PubMed]
- Faraji, F.; Ramirez, S.I.; Anguiano Quiroz, P.Y.; Mendez-Molina, A.N.; Gutkind, J.S. Genomic Hippo Pathway Alterations and Persistent YAP/TAZ Activation: New Hallmarks in Head and Neck Cancer. Cells 2022, 11, 1370. [Google Scholar] [CrossRef] [PubMed]
- Lengel, H.B.; Mastrogiacomo, B.; Connolly, J.G.; Tan, K.S.; Liu, Y.; Fick, C.N.; Dunne, E.G.; He, D.; Lankadasari, M.B.; Satravada, B.A.; et al. Genomic mapping of metastatic organotropism in lung adenocarcinoma. Cancer Cell 2023, 41, 970–985.e3. [Google Scholar] [CrossRef] [PubMed]
- Shih, D.J.H.; Nayyar, N.; Bihun, I.; Dagogo-Jack, I.; Gill, C.M.; Aquilanti, E.; Bertalan, M.; Kaplan, A.; D’Andrea, M.R.; Chukwueke, U.; et al. Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma. Nat. Genet. 2020, 52, 371–377. [Google Scholar] [CrossRef] [PubMed]
- Tanas, M.R.; Sboner, A.; Oliveira, A.M.; Erickson-Johnson, M.R.; Hespelt, J.; Hanwright, P.J.; Flanagan, J.; Luo, Y.; Fenwick, K.; Natrajan, R.; et al. Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. Sci. Transl. Med. 2011, 3, 98ra82. [Google Scholar] [CrossRef]
- Seavey, C.N.; Pobbati, A.V.; Hallett, A.; Ma, S.; Reynolds, J.P.; Kanai, R.; Lamar, J.M.; Rubin, B.P. WWTR1(TAZ)-CAMTA1 gene fusion is sufficient to dysregulate YAP/TAZ signaling and drive epithelioid hemangioendothelioma tumorigenesis. Genes. Dev. 2021, 35, 512–527. [Google Scholar] [CrossRef]
- Driskill, J.H.; Zheng, Y.; Wu, B.K.; Wang, L.; Cai, J.; Rakheja, D.; Dellinger, M.; Pan, D. WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma. Genes. Dev. 2021, 35, 495–511. [Google Scholar] [CrossRef] [PubMed]
- Szulzewsky, F.; Arora, S.; Hoellerbauer, P.; King, C.; Nathan, E.; Chan, M.; Cimino, P.J.; Ozawa, T.; Kawauchi, D.; Pajtler, K.W.; et al. Comparison of tumor-associated YAP1 fusions identifies a recurrent set of functions critical for oncogenesis. Genes. Dev. 2020, 34, 1051–1064. [Google Scholar] [CrossRef]
- Lin, L.; Sabnis, A.J.; Chan, E.; Olivas, V.; Cade, L.; Pazarentzos, E.; Asthana, S.; Neel, D.; Yan, J.J.; Lu, X.; et al. The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies. Nat. Genet. 2015, 47, 250–256. [Google Scholar] [CrossRef]
- Gao, R.; Kalathur, R.K.R.; Coto-Llerena, M.; Ercan, C.; Buechel, D.; Shuang, S.; Piscuoglio, S.; Dill, M.T.; Camargo, F.D.; Christofori, G.; et al. YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis. EMBO Mol. Med. 2021, 13, e14351. [Google Scholar] [CrossRef]
- Shibue, T.; Weinberg, R.A. EMT, CSCs, and drug resistance: The mechanistic link and clinical implications. Nat. Rev. Clin. Oncol. 2017, 14, 611–629. [Google Scholar] [CrossRef]
- Pastushenko, I.; Blanpain, C. EMT Transition States during Tumor Progression and Metastasis. Trends Cell Biol. 2019, 29, 212–226. [Google Scholar] [CrossRef]
- Matteucci, E.; Maroni, P.; Luzzati, A.; Perrucchini, G.; Bendinelli, P.; Desiderio, M.A. Bone metastatic process of breast cancer involves methylation state affecting E-cadherin expression through TAZ and WWOX nuclear effectors. Eur. J. Cancer 2013, 49, 231–244. [Google Scholar] [CrossRef] [PubMed]
- Lei, Q.Y.; Zhang, H.; Zhao, B.; Zha, Z.Y.; Bai, F.; Pei, X.H.; Zhao, S.; Xiong, Y.; Guan, K.L. TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway. Mol. Cell Biol. 2008, 28, 2426–2436. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.; Wang, Y.; Zhu, Y.; Yuan, C.; Wang, D.; Zhang, W.; Qi, B.; Qiu, J.; Song, X.; Ye, J.; et al. The Hippo transducer TAZ promotes epithelial to mesenchymal transition and cancer stem cell maintenance in oral cancer. Mol. Oncol. 2015, 9, 1091–1105. [Google Scholar] [CrossRef] [PubMed]
- Shao, D.D.; Xue, W.; Krall, E.B.; Bhutkar, A.; Piccioni, F.; Wang, X.; Schinzel, A.C.; Sood, S.; Rosenbluh, J.; Kim, J.W.; et al. KRAS and YAP1 converge to regulate EMT and tumor survival. Cell 2014, 158, 171–184. [Google Scholar] [CrossRef]
- Lau, A.N.; Curtis, S.J.; Fillmore, C.M.; Rowbotham, S.P.; Mohseni, M.; Wagner, D.E.; Beede, A.M.; Montoro, D.T.; Sinkevicius, K.W.; Walton, Z.E.; et al. Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis. EMBO J. 2014, 33, 468–481. [Google Scholar] [CrossRef]
- Sun, D.; Li, X.; He, Y.; Li, W.; Wang, Y.; Wang, H.; Jiang, S.; Xin, Y. YAP1 enhances cell proliferation, migration, and invasion of gastric cancer in vitro and in vivo. Oncotarget 2016, 7, 81062–81076. [Google Scholar] [CrossRef]
- Yin, K.; Dang, S.; Cui, L.; Fan, X.; Wang, L.; Xie, R.; Qu, J.; Shang, M.; Chen, J.; Xu, Z. Netrin-1 promotes metastasis of gastric cancer by regulating YAP activity. Biochem. Biophys. Res. Commun. 2018, 496, 76–82. [Google Scholar] [CrossRef]
- Huang, J.L.; Urtatiz, O.; Van Raamsdonk, C.D. Oncogenic G Protein GNAQ Induces Uveal Melanoma and Intravasation in Mice. Cancer Res. 2015, 75, 3384–3397. [Google Scholar] [CrossRef]
- Sharif, G.M.; Schmidt, M.O.; Yi, C.; Hu, Z.; Haddad, B.R.; Glasgow, E.; Riegel, A.T.; Wellstein, A. Cell growth density modulates cancer cell vascular invasion via Hippo pathway activity and CXCR2 signaling. Oncogene 2015, 34, 5879–5889. [Google Scholar] [CrossRef]
- Benjamin, D.C.; Kang, J.H.; Hamza, B.; King, E.M.; Lamar, J.M.; Manalis, S.R.; Hynes, R.O. YAP Enhances Tumor Cell Dissemination by Promoting Intravascular Motility and Reentry into Systemic Circulation. Cancer Res. 2020, 80, 3867–3879. [Google Scholar] [CrossRef] [PubMed]
- Ortega, A.; Vera, I.; Diaz, M.P.; Navarro, C.; Rojas, M.; Torres, W.; Parra, H.; Salazar, J.; De Sanctis, J.B.; Bermudez, V. The YAP/TAZ Signaling Pathway in the Tumor Microenvironment and Carcinogenesis: Current Knowledge and Therapeutic Promises. Int. J. Mol. Sci. 2021, 23, 430. [Google Scholar] [CrossRef]
- Mokhtari, R.B.; Ashayeri, N.; Baghaie, L.; Sambi, M.; Satari, K.; Baluch, N.; Bosykh, D.A.; Szewczuk, M.R.; Chakraborty, S. The Hippo Pathway Effectors YAP/TAZ-TEAD Oncoproteins as Emerging Therapeutic Targets in the Tumor Microenvironment. Cancers 2023, 15, 3468. [Google Scholar] [CrossRef]
- Wang, Z.; Wang, F.; Ding, X.Y.; Li, T.E.; Wang, H.Y.; Gao, Y.H.; Wang, W.J.; Liu, Y.F.; Chen, X.S.; Shen, K.W. Hippo/YAP signaling choreographs the tumor immune microenvironment to promote triple negative breast cancer progression via TAZ/IL-34 axis. Cancer Lett. 2022, 527, 174–190. [Google Scholar] [CrossRef] [PubMed]
- Uemura, N.; Hayashi, H.; Liu, Z.; Matsumura, K.; Ogata, Y.; Yasuda, N.; Sato, H.; Shiraishi, Y.; Miyata, T.; Nakagawa, S.; et al. Statins exert anti-growth effects by suppressing YAP/TAZ expressions via JNK signal activation and eliminate the immune suppression by downregulating PD-L1 expression in pancreatic cancer. Am. J. Cancer Res. 2023, 13, 2041–2054. [Google Scholar]
- Pan, Z.; Tian, Y.; Cao, C.; Niu, G. The Emerging Role of YAP/TAZ in Tumor Immunity. Mol. Cancer Res. 2019, 17, 1777–1786. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.; McAndrews, K.M.; Kalluri, R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat. Rev. Clin. Oncol. 2021, 18, 792–804. [Google Scholar] [CrossRef]
- Calvo, F.; Ege, N.; Grande-Garcia, A.; Hooper, S.; Jenkins, R.P.; Chaudhry, S.I.; Harrington, K.; Williamson, P.; Moeendarbary, E.; Charras, G.; et al. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat. Cell Biol. 2013, 15, 637–646. [Google Scholar] [CrossRef] [PubMed]
- Foster, C.T.; Gualdrini, F.; Treisman, R. Mutual dependence of the MRTF-SRF and YAP-TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics. Genes. Dev. 2017, 31, 2361–2375. [Google Scholar] [CrossRef]
- Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef]
- Er, E.E.; Valiente, M.; Ganesh, K.; Zou, Y.; Agrawal, S.; Hu, J.; Griscom, B.; Rosenblum, M.; Boire, A.; Brogi, E.; et al. Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization. Nat. Cell Biol. 2018, 20, 966–978. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Rouse, C.; Jasper, J.S.; Pendergast, A.M. ABL kinases promote breast cancer osteolytic metastasis by modulating tumor-bone interactions through TAZ and STAT5 signaling. Sci. Signal 2016, 9, ra12. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Wang, S.; Xing, Z.; Lin, A.; Liang, K.; Song, J.; Hu, Q.; Yao, J.; Chen, Z.; Park, P.K.; et al. A ROR1-HER3-lncRNA signalling axis modulates the Hippo-YAP pathway to regulate bone metastasis. Nat. Cell Biol. 2017, 19, 106–119. [Google Scholar] [CrossRef] [PubMed]
- Bartucci, M.; Dattilo, R.; Moriconi, C.; Pagliuca, A.; Mottolese, M.; Federici, G.; Benedetto, A.D.; Todaro, M.; Stassi, G.; Sperati, F.; et al. TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells. Oncogene 2015, 34, 681–690. [Google Scholar] [CrossRef]
- Lin, C.H.; Pelissier, F.A.; Zhang, H.; Lakins, J.; Weaver, V.M.; Park, C.; LaBarge, M.A. Microenvironment rigidity modulates responses to the HER2 receptor tyrosine kinase inhibitor lapatinib via YAP and TAZ transcription factors. Mol. Biol. Cell 2015, 26, 3946–3953. [Google Scholar] [CrossRef]
- Kim, M.H.; Kim, J.; Hong, H.; Lee, S.H.; Lee, J.K.; Jung, E.; Kim, J. Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation. EMBO J. 2016, 35, 462–478. [Google Scholar] [CrossRef] [PubMed]
- Fernandez, L.A.; Squatrito, M.; Northcott, P.; Awan, A.; Holland, E.C.; Taylor, M.D.; Nahle, Z.; Kenney, A.M. Oncogenic YAP promotes radioresistance and genomic instability in medulloblastoma through IGF2-mediated Akt activation. Oncogene 2012, 31, 1923–1937. [Google Scholar] [CrossRef]
- Cheng, H.; Zhang, Z.; Rodriguez-Barrueco, R.; Borczuk, A.; Liu, H.; Yu, J.; Silva, J.M.; Cheng, S.K.; Perez-Soler, R.; Halmos, B. Functional genomics screen identifies YAP1 as a key determinant to enhance treatment sensitivity in lung cancer cells. Oncotarget 2016, 7, 28976–28988. [Google Scholar] [CrossRef]
- Mudianto, T.; Campbell, K.M.; Webb, J.; Zolkind, P.; Skidmore, Z.L.; Riley, R.; Barnell, E.K.; Ozgenc, I.; Giri, T.; Dunn, G.P.; et al. Yap1 Mediates Trametinib Resistance in Head and Neck Squamous Cell Carcinomas. Clin. Cancer Res. 2021, 27, 2326–2339. [Google Scholar] [CrossRef]
- Hagenbeek, T.J.; Zbieg, J.R.; Hafner, M.; Mroue, R.; Lacap, J.A.; Sodir, N.M.; Noland, C.L.; Afghani, S.; Kishore, A.; Bhat, K.P.; et al. An allosteric pan-TEAD inhibitor blocks oncogenic YAP/TAZ signaling and overcomes KRAS G12C inhibitor resistance. Nat. Cancer 2023, 4, 812–828. [Google Scholar] [CrossRef]
- Panciera, T.; Azzolin, L.; Fujimura, A.; Di Biagio, D.; Frasson, C.; Bresolin, S.; Soligo, S.; Basso, G.; Bicciato, S.; Rosato, A.; et al. Induction of Expandable Tissue-Specific Stem/Progenitor Cells through Transient Expression of YAP/TAZ. Cell Stem Cell 2016, 19, 725–737. [Google Scholar] [CrossRef] [PubMed]
- Castellan, M.; Guarnieri, A.; Fujimura, A.; Zanconato, F.; Battilana, G.; Panciera, T.; Sladitschek, H.L.; Contessotto, P.; Citron, A.; Grilli, A.; et al. Single-cell analyses reveal YAP/TAZ as regulators of stemness and cell plasticity in Glioblastoma. Nat. Cancer 2021, 2, 174–188. [Google Scholar] [CrossRef] [PubMed]
- Fisher, M.L.; Grun, D.; Adhikary, G.; Xu, W.; Eckert, R.L. Inhibition of YAP function overcomes BRAF inhibitor resistance in melanoma cancer stem cells. Oncotarget 2017, 8, 110257–110272. [Google Scholar] [CrossRef] [PubMed]
- Qiao, Y.; Chen, J.; Lim, Y.B.; Finch-Edmondson, M.L.; Seshachalam, V.P.; Qin, L.; Jiang, T.; Low, B.C.; Singh, H.; Lim, C.T.; et al. YAP Regulates Actin Dynamics through ARHGAP29 and Promotes Metastasis. Cell Rep. 2017, 19, 1495–1502. [Google Scholar] [CrossRef] [PubMed]
- Xu, M.Z.; Chan, S.W.; Liu, A.M.; Wong, K.F.; Fan, S.T.; Chen, J.; Poon, R.T.; Zender, L.; Lowe, S.W.; Hong, W.; et al. AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma. Oncogene 2011, 30, 1229–1240. [Google Scholar] [CrossRef]
- Tanaka, K.; Osada, H.; Murakami-Tonami, Y.; Horio, Y.; Hida, T.; Sekido, Y. Statin suppresses Hippo pathway-inactivated malignant mesothelioma cells and blocks the YAP/CD44 growth stimulatory axis. Cancer Lett. 2017, 385, 215–224. [Google Scholar] [CrossRef]
- Li, W.; Cao, Y.; Xu, J.; Wang, Y.; Li, W.; Wang, Q.; Hu, Z.; Hao, Y.; Hu, L.; Sun, Y.; et al. YAP transcriptionally regulates COX-2 expression and GCCSysm-4 (G-4), a dual YAP/COX-2 inhibitor, overcomes drug resistance in colorectal cancer. J. Exp. Clin. Cancer Res. 2017, 36, 144. [Google Scholar] [CrossRef]
- Zhao, B.; Ye, X.; Yu, J.; Li, L.; Li, W.; Li, S.; Yu, J.; Lin, J.D.; Wang, C.Y.; Chinnaiyan, A.M.; et al. TEAD mediates YAP-dependent gene induction and growth control. Genes. Dev. 2008, 22, 1962–1971. [Google Scholar] [CrossRef]
- Zhang, H.; Liu, C.Y.; Zha, Z.Y.; Zhao, B.; Yao, J.; Zhao, S.; Xiong, Y.; Lei, Q.Y.; Guan, K.L. TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition. J. Biol. Chem. 2009, 284, 13355–13362. [Google Scholar] [CrossRef]
- Zhou, Y.; Huang, T.; Cheng, A.S.; Yu, J.; Kang, W.; To, K.F. The TEAD Family and Its Oncogenic Role in Promoting Tumorigenesis. Int. J. Mol. Sci. 2016, 17, 138. [Google Scholar] [CrossRef]
- Lai, D.; Ho, K.C.; Hao, Y.; Yang, X. Taxol resistance in breast cancer cells is mediated by the hippo pathway component TAZ and its downstream transcriptional targets Cyr61 and CTGF. Cancer Res. 2011, 71, 2728–2738. [Google Scholar] [CrossRef] [PubMed]
- Mizuno, T.; Murakami, H.; Fujii, M.; Ishiguro, F.; Tanaka, I.; Kondo, Y.; Akatsuka, S.; Toyokuni, S.; Yokoi, K.; Osada, H.; et al. YAP induces malignant mesothelioma cell proliferation by upregulating transcription of cell cycle-promoting genes. Oncogene 2012, 31, 5117–5122. [Google Scholar] [CrossRef] [PubMed]
- Weiler, S.M.E.; Lutz, T.; Bissinger, M.; Sticht, C.; Knaub, M.; Gretz, N.; Schirmacher, P.; Breuhahn, K. TAZ target gene ITGAV regulates invasion and feeds back positively on YAP and TAZ in liver cancer cells. Cancer Lett. 2020, 473, 164–175. [Google Scholar] [CrossRef]
- Ren, Y.R.; Patel, K.; Paun, B.C.; Kern, S.E. Structural analysis of the cancer-specific promoter in mesothelin and in other genes overexpressed in cancers. J. Biol. Chem. 2011, 286, 11960–11969. [Google Scholar] [CrossRef] [PubMed]
- Zanconato, F.; Forcato, M.; Battilana, G.; Azzolin, L.; Quaranta, E.; Bodega, B.; Rosato, A.; Bicciato, S.; Cordenonsi, M.; Piccolo, S. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat. Cell Biol. 2015, 17, 1218–1227. [Google Scholar] [CrossRef] [PubMed]
- Janse van Rensburg, H.J.; Azad, T.; Ling, M.; Hao, Y.; Snetsinger, B.; Khanal, P.; Minassian, L.M.; Graham, C.H.; Rauh, M.J.; Yang, X. The Hippo Pathway Component TAZ Promotes Immune Evasion in Human Cancer through PD-L1. Cancer Res. 2018, 78, 1457–1470. [Google Scholar] [CrossRef]
- Wang, Z.; Wu, Y.; Wang, H.; Zhang, Y.; Mei, L.; Fang, X.; Zhang, X.; Zhang, F.; Chen, H.; Liu, Y.; et al. Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility. Proc. Natl. Acad. Sci. USA 2014, 111, E89–E98. [Google Scholar] [CrossRef]
- Shen, J.; Cao, B.; Wang, Y.; Ma, C.; Zeng, Z.; Liu, L.; Li, X.; Tao, D.; Gong, J.; Xie, D. Hippo component YAP promotes focal adhesion and tumour aggressiveness via transcriptionally activating THBS1/FAK signalling in breast cancer. J. Exp. Clin. Cancer Res. 2018, 37, 175. [Google Scholar] [CrossRef]
- Lamhamedi-Cherradi, S.E.; Mohiuddin, S.; Mishra, D.K.; Krishnan, S.; Velasco, A.R.; Vetter, A.M.; Pence, K.; McCall, D.; Truong, D.D.; Cuglievan, B.; et al. Transcriptional activators YAP/TAZ and AXL orchestrate dedifferentiation, cell fate, and metastasis in human osteosarcoma. Cancer Gene Ther. 2021, 28, 1325–1338. [Google Scholar] [CrossRef]
- Ghiso, E.; Migliore, C.; Ciciriello, V.; Morando, E.; Petrelli, A.; Corso, S.; De Luca, E.; Gatti, G.; Volante, M.; Giordano, S. YAP-Dependent AXL Overexpression Mediates Resistance to EGFR Inhibitors in NSCLC. Neoplasia 2017, 19, 1012–1021. [Google Scholar] [CrossRef]
- Zhang, X.; Yang, L.; Szeto, P.; Abali, G.K.; Zhang, Y.; Kulkarni, A.; Amarasinghe, K.; Li, J.; Vergara, I.A.; Molania, R.; et al. The Hippo pathway oncoprotein YAP promotes melanoma cell invasion and spontaneous metastasis. Oncogene 2020, 39, 5267–5281. [Google Scholar] [CrossRef]
- Hsia, D.A.; Mitra, S.K.; Hauck, C.R.; Streblow, D.N.; Nelson, J.A.; Ilic, D.; Huang, S.; Li, E.; Nemerow, G.R.; Leng, J.; et al. Differential regulation of cell motility and invasion by FAK. J. Cell Biol. 2003, 160, 753–767. [Google Scholar] [CrossRef] [PubMed]
- Cheuk, I.W.; Siu, M.T.; Ho, J.C.; Chen, J.; Shin, V.Y.; Kwong, A. ITGAV targeting as a therapeutic approach for treatment of metastatic breast cancer. Am. J. Cancer Res. 2020, 10, 211–223. [Google Scholar]
- Chen, P.S.; Wang, M.Y.; Wu, S.N.; Su, J.L.; Hong, C.C.; Chuang, S.E.; Chen, M.W.; Hua, K.T.; Wu, Y.L.; Cha, S.T.; et al. CTGF enhances the motility of breast cancer cells via an integrin-alphavbeta3-ERK1/2-dependent S100A4-upregulated pathway. J. Cell Sci. 2007, 120, 2053–2065. [Google Scholar] [CrossRef] [PubMed]
- Hou, C.H.; Lin, F.L.; Hou, S.M.; Liu, J.F. Cyr61 promotes epithelial-mesenchymal transition and tumor metastasis of osteosarcoma by Raf-1/MEK/ERK/Elk-1/TWIST-1 signaling pathway. Mol. Cancer 2014, 13, 236. [Google Scholar] [CrossRef] [PubMed]
- Wierstra, I. FOXM1 (Forkhead box M1) in tumorigenesis: Overexpression in human cancer, implication in tumorigenesis, oncogenic functions, tumor-suppressive properties, and target of anticancer therapy. Adv. Cancer Res. 2013, 119, 191–419. [Google Scholar] [CrossRef] [PubMed]
- Koo, C.Y.; Muir, K.W.; Lam, E.W. FOXM1: From cancer initiation to progression and treatment. Biochim. Biophys. Acta 2012, 1819, 28–37. [Google Scholar] [CrossRef]
- Liao, G.B.; Li, X.Z.; Zeng, S.; Liu, C.; Yang, S.M.; Yang, L.; Hu, C.J.; Bai, J.Y. Regulation of the master regulator FOXM1 in cancer. Cell Commun. Signal 2018, 16, 57. [Google Scholar] [CrossRef]
- Chu, X.Y.; Zhu, Z.M.; Chen, L.B.; Wang, J.H.; Su, Q.S.; Yang, J.R.; Lin, Y.; Xue, L.J.; Liu, X.B.; Mo, X.B. FOXM1 expression correlates with tumor invasion and a poor prognosis of colorectal cancer. Acta Histochem. 2012, 114, 755–762. [Google Scholar] [CrossRef]
- Abdeljaoued, S.; Bettaieb, I.; Nasri, M.; Adouni, O.; Goucha, A.; El Amine, O.; Boussen, H.; Rahal, K.; Gamoudi, A. Overexpression of FOXM1 Is a Potential Prognostic Marker in Male Breast Cancer. Oncol. Res. Treat. 2017, 40, 167–172. [Google Scholar] [CrossRef]
- Li, H.L.; Li, Q.Y.; Jin, M.J.; Lu, C.F.; Mu, Z.Y.; Xu, W.Y.; Song, J.; Zhang, Y.; Zhang, S.Y. A review: Hippo signaling pathway promotes tumor invasion and metastasis by regulating target gene expression. J. Cancer Res. Clin. Oncol. 2021, 147, 1569–1585. [Google Scholar] [CrossRef] [PubMed]
- Hassan, R.; Bera, T.; Pastan, I. Mesothelin: A new target for immunotherapy. Clin. Cancer Res. 2004, 10, 3937–3942. [Google Scholar] [CrossRef] [PubMed]
- Jewell, M.L.; Gibson, J.R.; Guy, C.D.; Hyun, J.; Du, K.; Oh, S.H.; Premont, R.T.; Hsu, D.S.; Ribar, T.; Gregory, S.G.; et al. Single-Cell RNA Sequencing Identifies Yes-Associated Protein 1-Dependent Hepatic Mesothelial Progenitors in Fibrolamellar Carcinoma. Am. J. Pathol. 2020, 190, 93–107. [Google Scholar] [CrossRef] [PubMed]
- Chang, M.C.; Chen, C.A.; Chen, P.J.; Chiang, Y.C.; Chen, Y.L.; Mao, T.L.; Lin, H.W.; Lin Chiang, W.H.; Cheng, W.F. Mesothelin enhances invasion of ovarian cancer by inducing MMP-7 through MAPK/ERK and JNK pathways. Biochem. J. 2012, 442, 293–302. [Google Scholar] [CrossRef]
- Rump, A.; Morikawa, Y.; Tanaka, M.; Minami, S.; Umesaki, N.; Takeuchi, M.; Miyajima, A. Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J. Biol. Chem. 2004, 279, 9190–9198. [Google Scholar] [CrossRef]
- Zhang, S.; Chang, M.C.; Zylka, D.; Turley, S.; Harrison, R.; Turley, E.A. The hyaluronan receptor RHAMM regulates extracellular-regulated kinase. J. Biol. Chem. 1998, 273, 11342–11348. [Google Scholar] [CrossRef]
- Tao, Z.; Wu, X. Targeting Transcription Factors in Cancer: From “Undruggable” to “Druggable”. Methods Mol. Biol. 2023, 2594, 107–131. [Google Scholar] [CrossRef]
- Macleod, A.R. Abstract ND11: The discovery and characterization of ION-537: A next generation antisense oligonucleotide inhibitor of YAP1 in preclinical cancer models. Cancer Res. 2021, 81, ND11. [Google Scholar] [CrossRef]
- Liu-Chittenden, Y.; Huang, B.; Shim, J.S.; Chen, Q.; Lee, S.J.; Anders, R.A.; Liu, J.O.; Pan, D. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes. Dev. 2012, 26, 1300–1305. [Google Scholar] [CrossRef]
- Furet, P.; Bordas, V.; Le Douget, M.; Salem, B.; Mesrouze, Y.; Imbach-Weese, P.; Sellner, H.; Voegtle, M.; Soldermann, N.; Chapeau, E.; et al. The First Class of Small Molecules Potently Disrupting the YAP-TEAD Interaction by Direct Competition. ChemMedChem 2022, 17, e202200303. [Google Scholar] [CrossRef]
- Li, Y.; Liu, S.; Ng, E.Y.; Li, R.; Poulsen, A.; Hill, J.; Pobbati, A.V.; Hung, A.W.; Hong, W.; Keller, T.H.; et al. Structural and ligand-binding analysis of the YAP-binding domain of transcription factor TEAD4. Biochem. J. 2018, 475, 2043–2055. [Google Scholar] [CrossRef]
- Pobbati, A.V.; Han, X.; Hung, A.W.; Weiguang, S.; Huda, N.; Chen, G.Y.; Kang, C.; Chia, C.S.; Luo, X.; Hong, W.; et al. Targeting the Central Pocket in Human Transcription Factor TEAD as a Potential Cancer Therapeutic Strategy. Structure 2015, 23, 2076–2086. [Google Scholar] [CrossRef]
- Tang, T.T.; Post, L. The TEAD autopalmitoylation inhibitor VT3989 improves efficacy and increases durability of efficacy of osimertinib in preclinical EGFR mutant tumor models. Cancer Res. 2022, 82, 5364. [Google Scholar] [CrossRef]
- Kaneda, A.; Seike, T.; Danjo, T.; Nakajima, T.; Otsubo, N.; Yamaguchi, D.; Tsuji, Y.; Hamaguchi, K.; Yasunaga, M.; Nishiya, Y.; et al. The novel potent TEAD inhibitor, K-975, inhibits YAP1/TAZ-TEAD protein-protein interactions and exerts an anti-tumor effect on malignant pleural mesothelioma. Am. J. Cancer Res. 2020, 10, 4399–4415. [Google Scholar]
- Li, Q.; Sun, Y.; Jarugumilli, G.K.; Liu, S.; Dang, K.; Cotton, J.L.; Xiol, J.; Chan, P.Y.; DeRan, M.; Ma, L.; et al. Lats1/2 Sustain Intestinal Stem Cells and Wnt Activation through TEAD-Dependent and Independent Transcription. Cell Stem Cell 2020, 26, 675–692.e8. [Google Scholar] [CrossRef]
- Shorstova, T.; Foulkes, W.D.; Witcher, M. Achieving clinical success with BET inhibitors as anti-cancer agents. Br. J. Cancer 2021, 124, 1478–1490. [Google Scholar] [CrossRef]
- Martellucci, S.; Clementi, L.; Sabetta, S.; Mattei, V.; Botta, L.; Angelucci, A. Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned so Far. Cancers 2020, 12, 1448. [Google Scholar] [CrossRef]
- Rinaldi, C.; Wood, M.J.A. Antisense oligonucleotides: The next frontier for treatment of neurological disorders. Nat. Rev. Neurol. 2018, 14, 9–21. [Google Scholar] [CrossRef] [PubMed]
- Thompson, B.J. YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy. Bioessays 2020, 42, e1900162. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Zhu, X.; Feng, W.; Yu, Y.; Jeong, K.; Guo, W.; Lu, Y.; Mills, G.B. Verteporfin inhibits YAP function through up-regulating 14-3-3sigma sequestering YAP in the cytoplasm. Am. J. Cancer Res. 2016, 6, 27–37. [Google Scholar]
- Pobbati, A.V.; Rubin, B.P. Protein-Protein Interaction Disruptors of the YAP/TAZ-TEAD Transcriptional Complex. Molecules 2020, 25, 6001. [Google Scholar] [CrossRef]
- Chan, P.; Han, X.; Zheng, B.; DeRan, M.; Yu, J.; Jarugumilli, G.K.; Deng, H.; Pan, D.; Luo, X.; Wu, X. Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway. Nat. Chem. Biol. 2016, 12, 282–289. [Google Scholar] [CrossRef] [PubMed]
- Laraba, L.; Hillson, L.; de Guibert, J.G.; Hewitt, A.; Jaques, M.R.; Tang, T.T.; Post, L.; Ercolano, E.; Rai, G.; Yang, S.M.; et al. Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma. Brain 2023, 146, 1697–1713. [Google Scholar] [CrossRef] [PubMed]
- Tang, T.T.; Konradi, A.W.; Feng, Y.; Peng, X.; Ma, M.; Li, J.; Yu, F.X.; Guan, K.L.; Post, L. Small Molecule Inhibitors of TEAD Auto-palmitoylation Selectively Inhibit Proliferation and Tumor Growth of NF2-deficient Mesothelioma. Mol. Cancer Ther. 2021, 20, 986–998. [Google Scholar] [CrossRef]
- Kaneda, A.; Seike, T.; Uemori, T.; Myojo, K.; Aida, K.; Danjo, T.; Nakajima, T.; Yamaguchi, D.; Hamada, T.; Tsuji, Y. Discovery of a first-in-class TEAD inhibitor which directly inhibits YAP/TAZ-TEAD protein-protein interaction and shows a potent anti-tumor effect in malignant pleural mesothelioma. Cancer Res. 2019, 79, 3086. [Google Scholar] [CrossRef]
- Amidon, B.S.; Sanchez-Martin, M.; Bartolini, W.; Syed, S.; McGovern, K.; Xu, L.; Ecsedy, J.; Zhang, X.M.; Constan, A.; Castro, A.C. Abstract 2156: IK-930 is a novel TEAD inhibitor for the treatment of cancers harboring mutations in the Hippo signal transduction pathway. Cancer Res. 2022, 82, 2156. [Google Scholar] [CrossRef]
- Zanconato, F.; Battilana, G.; Forcato, M.; Filippi, L.; Azzolin, L.; Manfrin, A.; Quaranta, E.; Di Biagio, D.; Sigismondo, G.; Guzzardo, V.; et al. Transcriptional addiction in cancer cells is mediated by YAP/TAZ through BRD4. Nat. Med. 2018, 24, 1599–1610. [Google Scholar] [CrossRef]
- Kamide, D.; Yamashita, T.; Araki, K.; Tomifuji, M.; Tanaka, Y.; Tanaka, S.; Shiozawa, S.; Shiotani, A. Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model. Cancer Sci. 2016, 107, 666–673. [Google Scholar] [CrossRef]
- Keshet, R.; Adler, J.; Ricardo Lax, I.; Shanzer, M.; Porat, Z.; Reuven, N.; Shaul, Y. c-Abl antagonizes the YAP oncogenic function. Cell Death Differ. 2015, 22, 935–945. [Google Scholar] [CrossRef]
- Zucchini, C.; Manara, M.C.; Cristalli, C.; Carrabotta, M.; Greco, S.; Pinca, R.S.; Ferrari, C.; Landuzzi, L.; Pasello, M.; Lollini, P.L.; et al. ROCK2 deprivation leads to the inhibition of tumor growth and metastatic potential in osteosarcoma cells through the modulation of YAP activity. J. Exp. Clin. Cancer Res. 2019, 38, 503. [Google Scholar] [CrossRef] [PubMed]
- Battilana, G.; Zanconato, F.; Piccolo, S. Mechanisms of YAP/TAZ transcriptional control. Cell Stress. 2021, 5, 167–172. [Google Scholar] [CrossRef] [PubMed]
- Stein, C.; Bardet, A.F.; Roma, G.; Bergling, S.; Clay, I.; Ruchti, A.; Agarinis, C.; Schmelzle, T.; Bouwmeester, T.; Schubeler, D.; et al. YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers. PLoS Genet. 2015, 11, e1005465. [Google Scholar] [CrossRef] [PubMed]
Target Gene | Upstream Signaling Molecule | ChIP-qPCR | TEAD Binding Sites | Mechanism |
---|---|---|---|---|
ABL2 | TAZ | [52] | Yes [52] | Seeding Colonization |
ARHGAP29 | YAP | [105] | Yes [105] | Cell Motility Invasion |
AXL | YAP TAZ [52] | [106] | Yes [52,106] | Invasion Stemness Seeding Colonization Therapy Resistance |
CD44 | YAP | [107] | Yes [107] | Cell Motility Invasion |
COX-2 | YAP | [108] | Yes [108] | Cell Proliferation Colonization |
CTGF | YAP TAZ | YAP [109] TAZ [110] | Yes [111] | Cell Motility Invasion Therapy Resistance |
CYR61 | TAZ | [112] | Yes [111] | Cell Invasion EMT Therapy Resistance |
FOXM1 | YAP | [113] | Yes [113] | Cell Proliferation EMT Invasion |
ITGAV | TAZ | [114] | Yes [111] | Cell Motility Invasion |
L1CAM | TAZ | [52] | Yes [52] | Seeding Colonization Perivascular Extension |
MSLN | YAP | [115] | Yes [115] | Cell Motility Invasion |
MYC | YAP/TAZ | [116] | Yes [116] | Cell Growth |
PD-L1 | TAZ | [117] | Immune Evasion | |
RHAMM | YAP | [118] | Yes [118] | Cell Motility Invasion |
THBS1 | YAP | [119] | Yes [119] | Cell Motility Invasion |
Drug | Source (Company) | Target | Preclinical Studies | Clinical Trials |
---|---|---|---|---|
ION537 | Ionis Pharmaceuticals | Anti-YAP Antisense Oligonucleotide | [139] | Phase 1 Completed NCT04659096 (Advanced solid tumors) |
Verteporfin (Visudyne) | Novartis | YAP/TAZ and TEAD interaction inhibitor | [140] | Phase 1/2 Recruiting NCT04590664 (EGFR-mutated glioblastoma) |
IAG933 | Novartis | YAP/TAZ and TEAD interaction inhibitor | [141] | Phase 1 Recruiting NCT04857372 (Mesothelioma) |
Flufenamic acid | Commercially Available | TEAD palmitoylation inhibitor YAP/TAZ and TEAD interaction inhibitor | [142,143] | -- |
VT3989 | Vivace Therapeutics | TEAD palmitoylation inhibitor YAP/TAZ and TEAD interaction inhibitor | [144] | Phase 1 Recruiting NCT04665206 (Mesothelioma) |
K-975 | Kyowa Kirin (Tokyo, Japan) | TEAD palmitoylation inhibitor YAP/TAZ and TEAD interaction inhibitor | [145] | -- |
MGH-CP1 | Commercially Available | TEAD palmitoylation inhibitor YAP/TAZ and TEAD interaction inhibitor | [146] | -- |
IK-930 | Ikena Oncology | TEAD palmitoylation inhibitor YAP/TAZ and TEAD interaction inhibitor | -- | Phase 1 Recruiting NCT05228015 (Epithelioid hemangioendothelioma and mesothelioma) |
GNE-7883 | Genentech | Allosteric pan-TEAD Inhibitor | [101] | -- |
BET inhibitors | Multiple | BRD4 Inhibitor | Numerous Reviewed in [147] | Numerous Reviewed in [147] |
Dasatinib | Sprycel | SRC Inhibitor | Numerous Reviewed in [148] | Numerous Reviewed in [148] |
Asciminib (ABL001) | Novartis | ABL Inhibitor | [52] | -- |
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Thrash, H.L.; Pendergast, A.M. Multi-Functional Regulation by YAP/TAZ Signaling Networks in Tumor Progression and Metastasis. Cancers 2023, 15, 4701. https://doi.org/10.3390/cancers15194701
Thrash HL, Pendergast AM. Multi-Functional Regulation by YAP/TAZ Signaling Networks in Tumor Progression and Metastasis. Cancers. 2023; 15(19):4701. https://doi.org/10.3390/cancers15194701
Chicago/Turabian StyleThrash, Hannah L., and Ann Marie Pendergast. 2023. "Multi-Functional Regulation by YAP/TAZ Signaling Networks in Tumor Progression and Metastasis" Cancers 15, no. 19: 4701. https://doi.org/10.3390/cancers15194701