Opposing activities of the Ras and Hippo pathways converge on regulation of YAP protein turnover
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Cancer genomes accumulate numerous genetic and epigenetic modifications. Yet, human cellular transformation can be accomplished by a few genetically defined elements. These elements activate key pathways required to support replicative immortality and anchorage independent growth, a predictor of tumorigenesis in vivo. Here, we provide evidence that the Hippo tumor suppressor pathway is a key barrier to Ras-mediated cellular transformation. The Hippo pathway targets YAP1 for degradation via the βTrCP-SCF ubiquitin ligase complex. In contrast, the Ras pathway acts oppositely, to promote YAP1 stability through downregulation of the ubiquitin ligase complex substrate recognition factors SOCS5/6. Depletion of SOCS5/6 or upregulation of YAP1 can bypass the requirement for oncogenic Ras in anchorage independent growth in vitro and tumor formation in vivo. Through the YAP1 target, Amphiregulin, Ras activates the endogenous EGFR pathway, which is required for transformation. Thus, the oncogenic activity of Ras(V12) depends on its ability to counteract Hippo pathway activity, creating a positive feedback loop, which depends on stabilization of YAP1.
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Formation of context-dependent Yki/YAP-mediated signalling loops is a bona fide mechanism for tumour growth.
“The biological significance of our findings is validated by other studies that show formation of context-dependent Yki/YAP-mediated signalling loops as a bona fide mechanism for tumour growth (68,69).”
From A Tumour-Specific Molecular Network Promotes Tumour Growth in <i>Drosophila</i> by Enforcing a JNK-YKI Feedforward Loop (2023) · cites this paper as [69]
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1 retracted
Wang, L., Shi, S., Guo, Z., Zhang, X., Han, S., Yang, A., Wen, W., & Zhu, Q. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065539 · Cited by 266 · see citing works
RetractedComprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499 · see citing works
Role of YAP/TAZ in mechanotransduction
Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S., et al. (2011) · Nature · doi:10.1038/nature10137 · Cited by 5,979 · see citing works
Zhao, B., Wei, X., Li, W., Udan, R. S., Yang, Q., Kim, J., Xie, J., Ikenoue, T., Yu, J., Li, L., et al. (2007) · Genes & Development · doi:10.1101/gad.1602907 · Cited by 3,092 · see citing works
TEAD mediates YAP-dependent gene induction and growth control
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. (2008) · Genes & Development · doi:10.1101/gad.1664408 · Cited by 2,498 · see citing works
Elucidation of a universal size-control mechanism in Drosophila and mammals
Dong, J., Feldmann, G., Huang, J., Wu, S., Zhang, N., Comerford, S. A., Gayyed, M. F., Anders, R. A., Maitra, A., & Pan, D. (2007) · Cell · doi:10.1016/j.cell.2007.07.019 · Cited by 2,370 · see citing works
Creation of human tumour cells with defined genetic elements
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999) · Nature · doi:10.1038/22780 · Cited by 2,345 · see citing works
The Hippo Signaling Pathway in Development and Cancer
Pan, D. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.09.011 · Cited by 2,274 · see citing works
Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR
Prahallad, A., Sun, C., Huang, S., Di Nicolantonio, F., Salazar, R., Zecchin, D., Beijersbergen, R. L., Bardelli, A., & Bernards, R. (2012) · Nature · doi:10.1038/nature10868 · Cited by 2,051 · see citing works
The Hippo pathway and human cancer
Harvey, K. F., Zhang, X., & Thomas, D. M. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3458 · Cited by 1,852 · see citing works
Identification of a Chromosome 18q Gene that Is Altered in Colorectal Cancers
Fearon, E. R., Cho, K. R., Nigro, J. M., Kern, S. E., Simons, J. W., Ruppert, J. M., Hamilton, S. R., Preisinger, A. C., Thomas, G., Kinzler, K. W., et al. (1990) · Science · doi:10.1126/science.2294591 · Cited by 1,738 · see citing works
Liu-Chittenden, Y., Huang, B., Shim, J. S., Chen, Q., Lee, S.-J., Anders, R. A., Liu, J. O., & Pan, D. (2012) · Genes & Development · doi:10.1101/gad.192856.112 · Cited by 1,452 · see citing works
Self-citationA coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF <sup>β-TRCP</sup>
Zhao, B., Li, L., Tumaneng, K., Wang, C.-Y., & Guan, K.-L. (2010) · Genes & Development · doi:10.1101/gad.1843810 · Cited by 1,418 · see citing works
A Genetic Screen Implicates miRNA-372 and miRNA-373 As Oncogenes in Testicular Germ Cell Tumors
Voorhoeve, P. M., le Sage, C., Schrier, M., Gillis, A., Stoop, H., Nagel, R., Liu, Y. P., van Duijse, J., Drost, J., Griekspoor, A., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.037 · Cited by 1,263 · see citing works
Self-citationHippo Pathway Inhibits Wnt Signaling to Restrain Cardiomyocyte Proliferation and Heart Size
Heallen, T. R., Zhang, M., Wang, J., Bonilla-Claudio, M., Klysik, E., Johnson, R. L., & Martin, J. F. (2011) · Science · doi:10.1126/science.1199010 · Cited by 1,092 · see citing works
Lei, Q., Zhang, H., Zhao, B., Zha, Z., Bai, F., Pei, X., Zhao, S., Xiong, Y., & Guan, K. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01874-07 · Cited by 925 · see citing works
The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment
Johnson, R. L., & Halder, G. A. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4161 · Cited by 884 · see citing works
Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells
Elenbaas, B., Spirio, L., Koerner, F., Fleming, M. D., Zimonjic, D. B., Donaher, J. L., Popescu, N. C., Hahn, W. C., & Weinberg, R. A. (2001) · Genes & Development · doi:10.1101/gad.828901 · Cited by 878 · see citing works
Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP
Hao, Y., Chun, A., Cheung, K. J., Rashidi, B., & Yang, X. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m709037200 · Cited by 780 · see citing works
KRAS and YAP1 Converge to Regulate EMT and Tumor Survival
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. (2014) · Cell · doi:10.1016/j.cell.2014.06.004 · Cited by 744 · see citing works
Yap1 Activation Enables Bypass of Oncogenic Kras Addiction in Pancreatic Cancer
Kapoor, A., Yao, W., Ying, H., Hua, S., Liewen, A., Wang, Q., Zhong, Y., Wu, C.-J., Sadanandam, A., Hu, B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.003 · Cited by 716 · cited 1× · see citing works
“The other study found that the YAP locus was amplified in K-Ras induced pancreatic tumors that were able to regrow following removal of K-Ras expression (Kapoor et al , 2014).”
Enumeration of the Simian Virus 40 Early Region Elements Necessary for Human Cell Transformation
Hahn, W. C., Dessain, S. K., Brooks, M. W., King, J. E., Elenbaas, B., Sabatini, D. M., DeCaprio, J. A., & Weinberg, R. A. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.7.2111-2123.2002 · Cited by 603 · see citing works
Strohmaier, H. M., Spruck, C., Kaiser, P., Won, K., Sangfelt, O., & Reed, S. I. (2001) · Nature · doi:10.1038/35095076 · Cited by 584 · see citing works
Liu, C.-Y., Zha, Z.-Y., Zhou, X., Zhang, H., Huang, W., Zhao, D., Li, T., Chan, S. W., Lim, C. J., Hong, W., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.152942 · Cited by 525 · see citing works
Roles of F-box proteins in cancer
Wang, Z. P., Liu, P., Inuzuka, H., & Wei, W. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3700 · Cited by 516 · see citing works
Yin, F., Yu, J., Zheng, Y., Chen, Q., Zhang, N., & Pan, D. (2013) · Cell · doi:10.1016/j.cell.2013.08.025 · Cited by 506 · see citing works
Self-citationThe Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration programPreprint
Cai, J., Zhang, N., Zheng, Y., de Wilde, R. F., Maitra, A., & Pan, D. (2010) · Genes & Development · doi:10.1101/gad.1978810 · Cited by 491 · see citing works
Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines
Moberg, K. H., Bell, D. W., Wahrer, D. C. R., Haber, D. A., & Hariharan, I. K. (2001) · Nature · doi:10.1038/35095068 · Cited by 438 · see citing works
Zhang, J., Ji, J., Yu, M., Overholtzer, M., Smolen, G. A., Wang, R., Brugge, J. S., Dyson, N. J., & Haber, D. A. (2009) · Nature Cell Biology · doi:10.1038/ncb1993 · Cited by 427 · see citing works
Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene
Mao, J.-H., Perez-losada, J., Wu, D., DelRosario, R., Tsunematsu, R., Nakayama, K. I., Brown, K., Bryson, S., & Balmain, A. (2004) · Nature · doi:10.1038/nature03155 · Cited by 390 · see citing works
Role of protein ubiquitylation in regulating endocytosis of receptor tyrosine kinases
Marmor, M. D., & Yarden, Y. (2004) · Oncogene · doi:10.1038/sj.onc.1207390 · Cited by 382 · see citing works
Eser, S., Reiff, N., Messer, M., Seidler, B., Gottschalk, K., Dobler, M., Hieber, M., Arbeiter, A., Klein, S., Kong, B., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.01.023 · Cited by 360 · see citing works
Regulation of Hippo Signaling by EGFR-MAPK Signaling through Ajuba Family Proteins
Reddy, B. V. V. G., & Irvine, K. D. (2013) · Developmental Cell · doi:10.1016/j.devcel.2013.01.020 · Cited by 271 · see citing works
Chen, Q., Khoury, M., & Chen, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912274106 · Cited by 271 · see citing works
Self-citationBarry, E. R., & Camargo, F. D. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.12.006 · Cited by 214 · see citing works
Young, A., Lou, D., & McCormick, F. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0231 · Cited by 211 · see citing works
The tumor-suppressive functions of the human INK4A locus
Voorhoeve, P. M., & Agami, R. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00223-x · Cited by 194 · see citing works
Self-citationGaedcke, J., Grade, M., Jung, K., Camps, J., Jo, P., Emons, G., Gehoff, A., Sax, U., Schirmer, M., Becker, H., et al. (2010) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20811 · Cited by 187 · see citing works
TAZ Expression as a Prognostic Indicator in Colorectal Cancer
Yuen, H., McCrudden, C. M., Huang, Y., Tham, J. M., Zhang, X., Zeng, Q., Zhang, S., & Hong, W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054211 · Cited by 159 · see citing works
Loss of FBXW7, a cell cycle regulating gene, in colorectal cancer: Clinical significance
Iwatsuki, M., Mimori, K., Ishii, H., Yokobori, T., Takatsuno, Y., Sato, T., Toh, H., Onoyama, I., Nakayama, K. I., Baba, H. A., et al. (2009) · International Journal of Cancer · doi:10.1002/ijc.24879 · Cited by 143 · see citing works
Mutant K-Ras Activation of the Proapoptotic MST2 Pathway Is Antagonized by Wild-Type K-Ras
Matallanas, D., Romano, D., Al‐Mulla, F., O’Neill, E. E., Al-Ali, W., Crespo, P., Doyle, B. J., Nixon, C., Sansom, O. J., Drosten, M., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.10.016 · Cited by 133 · see citing works
The SOCS box—Adapting proteins for ubiquitination and proteasomal degradation
Linossi, E. M., & Nicholson, S. E. (2012) · IUBMB Life · doi:10.1002/iub.1011 · Cited by 122 · see citing works
Herranz, H., Hong, X., Hùng, N. T., Voorhoeve, P. M., & Cohen, S. M. (2012) · Genes & Development · doi:10.1101/gad.192021.112 · Cited by 74 · see citing works
Self-citationMolecular determinants of anti-EGFR sensitivity and resistance in metastatic colorectal cancer
Fiore, F. D., Sesboüé, R., Michel, P., Sabourin, J., & Frébourg, T. (2010) · British Journal of Cancer · doi:10.1038/sj.bjc.6606008 · Cited by 71 · see citing works
Qiu, X., Zheng, J., Guo, X., Gao, X., Liu, H., Tu, Y., & Zhang, Y. (2013) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1599-5 · Cited by 68 · see citing works
Ubiquitylation in immune disorders and cancer: from molecular mechanisms to therapeutic implications
Fulda, S., Rajalingam, K., & Đikić, I. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201100707 · Cited by 54 · see citing works
Expression of SOCSs in human prostate cancer and their association in prognosis
Zhu, J., Dai, Q.-S., Han, Z., He, H., Mo, R., Chen, G., Chen, Y., Wu, Y., Yang, S.-B., Jiang, F., et al. (2013) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1687-6 · Cited by 46 · see citing works
Immunopurification of Ago1 miRNPs selects for a distinct class of microRNA targets
Hong, X., Hammell, M., Ambros, V., & Cohen, S. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908149106 · Cited by 45 · see citing works
Self-citationAn update on targeting Hippo-YAP signaling in liver cancer
Liu, A. M., Xu, Z., & Luk, J. M. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2012.662958 · Cited by 32 · see citing works
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Misra, J. R., & Irvine, K. D. (2018) · Annual Review of Genetics · doi:10.1146/annurev-genet-120417-031621 · Cited by 496 · see citing works
Glycogen accumulation and phase separation drives liver tumor initiation
Liu, Q., Li, J., Zhang, W., Xiao, C., Zhang, S., Nian, C., Li, J., Su, D., Chen, L., Zhao, Q. C., et al. (2021) · Cell · doi:10.1016/j.cell.2021.10.001 · Cited by 312 · see citing works
Self-citationHe, C., Mao, D., Hua, G., Lv, X., Chen, X., Angeletti, P. C., Dong, J., Remmenga, S. W., Rodabaugh, K. J., Zhou, J. R., et al. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201404976 · Cited by 280 · see citing works
Song, S., Honjo, S., Jin, J., Chang, S.-S., Scott, A. W., Chen, Q., Kalhor, N., Correa, A. M., Hofstetter, W. L., Albarracin, C. T., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2191 · Cited by 274 · see citing works
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Kim, M. H., Kim, C. G., Kim, S.-K., Shin, S. J., Choe, E. A., Park, S.-H., Shin, E.-C., & Kim, J. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-17-0320 · Cited by 241 · see citing works
Gruber, R., Panayiotou, R., Nye, E. L., Spencer‐Dene, B., Stamp, G., & Behrens, A. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.05.006 · Cited by 214 · see citing works
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Rozengurt, E., Sinnett‐Smith, J. W., & Eibl, G. (2018) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-017-0005-2 · Cited by 135 · see citing works
Kaan, H. Y. K., Chan, S. W., Tan, S. K. J., Guo, F., Lim, C. J., Hong, W., & Song, H. (2017) · Scientific Reports · doi:10.1038/s41598-017-02219-9 · Cited by 111 · see citing works
Edwards, D. N., Ngwa, V. M., Wang, S., Shiuan, E., Brantley-Sieders, D. M., Kim, L. C., Reynolds, A. B., & Chen, J. (2017) · Science Signaling · doi:10.1126/scisignal.aan4667 · Cited by 44 · see citing works
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Zinatizadeh, M. R., Miri, S. R., Zarandi, P. K., Chalbatani, G. M., Rapôso, C., Mirzaei, H. R., Akbari, M. E., & Mahmoodzadeh, H. (2019) · Genes & Diseases · doi:10.1016/j.gendis.2019.11.003 · Cited by 94 · see citing works
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Coggins, G. E., Farrel, A., Rathi, K. S., Hayes, C. M., Scolaro, L., Rokita, J. L., & Maris, J. M. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-1415 · Cited by 66 · see citing works
Muranen, T. E., Selfors, L. M., Hwang, J., Gallegos, L. L., Coloff, J. L., Thoreen, C. C., Kang, S. A. W., Sabatini, D. M., Mills, G. B., & Brugge, J. S. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0155 · Cited by 66 · see citing works
Pham, T. H., Hagenbeek, T. J., Lee, H.-J., Li, J., Rose, C. M., Lin, E., Yu, M., Martin, S. E., Piskol, R., Lacap, J. A., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0706 · Cited by 64 · see citing works
Mayrhofer, M., Gourain, V., Reischl, M., Affaticati, P., Jenett, A., Joly, J., Benelli, M., Demichelis, F., Poliani, P. L., Sieger, D., et al. (2016) · Disease Models & Mechanisms · doi:10.1242/dmm.026500 · Cited by 64 · see citing works
Kandasamy, P., Zlobec, I., Nydegger, D. T., Pujol‐Giménez, J., Bhardwaj, R., Shirasawa, S., Tsunoda, T., & Hediger, M. A. (2021) · Molecular Oncology · doi:10.1002/1878-0261.12999 · Cited by 60 · see citing works
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Sero, J., & Bakal, C. (2017) · Cell Systems · doi:10.1016/j.cels.2016.11.015 · Cited by 56 · see citing works
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Kim, J. W., Berrios, C. J., Kim, M., Schade, A. E., Adelmant, G., Yeerna, H., Damato, E., Iniguez, A. B., Swanson, S. K., Florens, L. A., et al. (2020) · eLife · doi:10.7554/elife.53003 · Cited by 54 · see citing works
Herranz, H., Eichenlaub, T., & Cohen, S. M. (2016) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2015.11.037 · Cited by 49 · see citing works
Self-citationGNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers
Rasheed, S. A. K., Leong, H. S., Lakshmanan, M., Raju, A., Dadlani, D., Chong, F.-T., Shannon, N. B., Rajarethinam, R., Skanthakumar, T., Tan, E. Y., et al. (2017) · Oncogene · doi:10.1038/s41388-017-0038-6 · Cited by 51 · see citing works
Kahlhofer, J., & Teis, D. (2022) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13821 · Cited by 48 · see citing works
The roles of ubiquitin modifying enzymes in neoplastic disease
Kumari, N., Jaynes, P. W., Saei, A., Iyengar, P. V., Richard, J. L. C., & Eichhorn, P. J. A. (2017) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2017.09.002 · Cited by 49 · see citing works
Hippo‐Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior
van Soldt, B. J., & Cardoso, W. V. (2019) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.371 · Cited by 50 · see citing works
Targeting ubiquitination in disease and therapy
Yang, X., Lan, T., Zhang, B., Tao, X., Qi, W., Xie, K., Cai, Y., Liu, C., Han, J., & Wu, H. M. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02392-8 · Cited by 53 · see citing works
Troilo, A., Benson, E. K., Esposito, D., Garibsingh, R. A., Reddy, E. P., Mungamuri, S. K., & Aaronson, S. A. (2016) · Oncotarget · doi:10.18632/oncotarget.9117 · Cited by 46 · see citing works
Gopal, U., Mowery, Y. M., Young, K. H., & Pizzo, S. V. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.009091 · Cited by 46 · see citing works
Qian, F., Xiao, J., Gai, L., & Zhu, J. (2018) · Molecular Carcinogenesis · doi:10.1002/mc.22944 · Cited by 45 · see citing works
Hippo Reprograms the Transcriptional Response to Ras Signaling
Pascual, J., Jacobs, J., Sansores-García, L., Natarajan, M., Zeitlinger, J., Aerts, S., Halder, G. A., & Hamaratoǧlu, F. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.08.013 · Cited by 42 · see citing works
Seviour, E. G., Sehgal, V., Mishra, D. K., Rupaimoole, R., Rodriguez‐Aguayo, C., Lopez‐Berestein, G., Lee, J. S., Sood, A. K., Kim, M. P., Mills, G. B., et al. (2016) · Oncogene · doi:10.1038/onc.2016.308 · Cited by 42 · see citing works
Nguyen, T., Andrējeva, D., Gupta, R., Choudhary, C., Hong, X., Eichhorn, P. J. A., Loya, A. C., & Cohen, S. M. (2016) · Cell Discovery · doi:10.1038/celldisc.2016.1 · Cited by 41 · see citing works
Self-citationLi, Z., Liu, X., Yu, H., Wang, S., Zhao, S., & Jiang, G. (2021) · Human Cell · doi:10.1007/s13577-021-00650-9 · Cited by 38 · see citing works
Novoplansky, O., Shnerb, A. B., Marripati, D., Jagadeeshan, S., Shareb, R. A., Conde‐López, C., Zorea, J., Prasad, M., Lulu, T. B., Yegodayev, K. M., et al. (2023) · Molecular Oncology · doi:10.1002/1878-0261.13500 · Cited by 37 · see citing works
A cell-autonomous tumour suppressor role of RAF1 in hepatocarcinogenesis
Jerić, I., Maurer, G., Cavallo, A. L., Raguz, J., Desideri, E., Tarkowski, B., Parrini, M., Fischer, I., Zatloukal, K., & Baccarini, M. (2016) · Nature Communications · doi:10.1038/ncomms13781 · Cited by 35 · see citing works
YAP ping about and not forgetting TAZ
Callus, B. A., Finch‐Edmondson, M., Fletcher, S., & Wilton, S. D. (2018) · FEBS Letters · doi:10.1002/1873-3468.13318 · Cited by 35 · see citing works
Keewan, E. F., & Matlawska‐Wasowska, K. (2021) · Cancers · doi:10.3390/cancers13164000 · Cited by 35 · see citing works
Kaan, H. Y. K., Sim, A. Y. L., Tan, S. K. J., Verma, C. S., & Song, H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0178381 · Cited by 35 · see citing works
Barzegari, A., Gueguen, V., Omidi, Y., Ostadrahimi, A., Nouri, M., & Pavon‐Djavid, G. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29455 · Cited by 34 · see citing works
Zou, Q., Liu, M., Liu, K., Zhang, Y., North, B. J., & Wang, B. (2023) · Cellular Oncology · doi:10.1007/s13402-023-00777-x · Cited by 33 · see citing works
Cell Density Regulates Cancer Metastasis Via the Hippo Pathway
Sharif, G. M., & Wellstein, A. (2015) · Future Oncology · doi:10.2217/fon.15.268 · Cited by 31 · see citing works
Thanasaksiri, K., Hırono, I., & Kondo, H. (2016) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2016.09.018 · Cited by 31 · see citing works
The Hippo–YAP Signaling as Guardian in the Pool of Intestinal Stem Cells
Seo, Y., Park, S., Kim, H., & Nam, J. (2020) · Biomedicines · doi:10.3390/biomedicines8120560 · Cited by 31 · see citing works
Nguyen, T., Kugler, J., & Cohen, S. M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0169587 · Cited by 30 · see citing works
Self-citationLü, T., Sun, L., & Zhu, X. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.06.031 · Cited by 29 · see citing works
Targeting Hippo signaling pathway by phytochemicals in cancer therapy
Moloudizargari, M., Asghari, M. H., Nabavi, S. F., Gulei, D., Berindan‐Neagoe, I., Bishayee, A., & Nabavi, S. M. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.05.005 · Cited by 28 · see citing works
Han, Y., Yu, C.-C., Fine, S. A., Youssof, A. L., Yang, Y., Yan, J., Karg, D. C., Cheung, E. C., Friedman, R. A., Ying, H., et al. (2021) · Oncogene · doi:10.1038/s41388-021-02040-9 · Cited by 28 · see citing works
Mutated HRAS Activates YAP1–AXL Signaling to Drive Metastasis of Head and Neck Cancer
Jagadeeshan, S., Prasad, M., Badarni, M., Lulu, T. B., Liju, V. B., Mathukkada, S., Saunders, C. J., Shnerb, A. B., Zorea, J., Yegodayev, K. M., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-2586 · Cited by 26 · see citing works
USP21 regulates Hippo pathway activity by mediating MARK protein turnover
Nguyen, T., Kugler, J., Loya, A. C., & Cohen, S. M. (2017) · Oncotarget · doi:10.18632/oncotarget.19322 · Cited by 25 · see citing works
Self-citationSun, X., Sun, Y., Li, J., Zhao, X., Shi, X., Gong, T., Pan, S., Zheng, Z., & Zhang, X. (2021) · Cancer Cell International · doi:10.1186/s12935-021-01859-2 · Cited by 23 · see citing works
Rozengurt, E., & Eibl, G. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i15.1797 · Cited by 22 · see citing works
Trentin, L., Bresolin, S., Giarin, E., Bardini, M., Serafin, V., Accordi, B., Fais, F., Tenca, C., Lorenzo, P. D., Valsecchi, M. G., et al. (2016) · Scientific Reports · doi:10.1038/srep34449 · Cited by 21 · see citing works
Chai, T. F., Manu, K. A., Casey, P. J., & Wang, M. (2020) · Oncogene · doi:10.1038/s41388-020-1364-7 · Cited by 20 · see citing works
The emerging roles of F-box proteins in pancreatic tumorigenesis
Wang, H., Maitra, A., & Wang, H. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.09.004 · Cited by 20 · see citing works
Breast Cancer: A Molecular and Redox Snapshot
Raman, D., Foo, C. H. J., Clement, M., & Pervaiz, S. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6546 · Cited by 20 · see citing works
Independent and core pathways in oncogenic KRAS signaling
Nussinov, R., Tsai, C., & Jang, H. (2016) · Expert Review of Proteomics · doi:10.1080/14789450.2016.1209417 · Cited by 20 · see citing works
Molecular evidence of field cancerization initiated by diabetes in colon cancer patients
del Puerto‐Nevado, L., Mínguez, P., Cortón, M., Casado, S. S., Prieto, I., Mas, S., Sanz, A. B., Gónzález-Alonso, P., Villaverde, C., Portal‐Núñez, S., et al. (2019) · Molecular Oncology · doi:10.1002/1878-0261.12438 · Cited by 19 · see citing works
TEAD Inhibitors Sensitize KRASG12C Inhibitors via Dual Cell Cycle Arrest in KRASG12C-Mutant NSCLC
Tammaccaro, S. L., Prigent, P., Le Bail, J.-C., Dos-Santos, O., Dassencourt, L., Eskandar, M., Buzy, A., Venier, O., Guillemot, J.-C., Veeranagouda, Y., et al. (2023) · Pharmaceuticals · doi:10.3390/ph16040553 · Cited by 18 · see citing works
The miRNAbantamregulates growth and tumorigenesis by repressing the cell cycle regulatortribbles
Gerlach, S. U., Sander, M., Song, S., & Herranz, H. (2019) · Life Science Alliance · doi:10.26508/lsa.201900381 · Cited by 18 · see citing works
The E3 ubiquitin ligase Slimb/β-TrCP is required for normal copper homeostasis in Drosophila
Zhang, B., Binks, T., & Burke, R. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2020.118768 · Cited by 16 · see citing works
Pharmacological strategies to target oncogenic KRAS signaling in pancreatic cancer
Chuang, H.-C., Huang, P.-H., Kulp, S. K., & Chen, C. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.01.006 · Cited by 16 · see citing works
Role and regulation of Yap in KrasG12D-induced lung cancer
Mao, Y., Sun, S., & Irvine, K. D. (2017) · Oncotarget · doi:10.18632/oncotarget.22865 · Cited by 16 · see citing works
Wang, Y., Wang, K., Fu, J., Zhang, Y., Mao, Y., Wang, X., Wang, X., Yu, R., & Zhou, X. (2022) · Neuro-Oncology · doi:10.1093/neuonc/noac156 · Cited by 15 · see citing works
Mu‐KRAS attenuates Hippo signaling pathway through PKCι to sustain the growth of pancreatic cancer
Wang, P., Zhang, H., Yang, J., Li, Z., Wang, Y., Leng, X., Ganapathy, S., Isakson, P., Chen, C., & Zhu, T. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28981 · Cited by 15 · see citing works
Yang, Z. P., Huang, S., & Zhao, L. (2022) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2022.02.001 · Cited by 14 · see citing works
The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer
Tu, Z., Schmoellerl, J., Mariani, O., Zheng, Y., Hu, Y. P., Vincent‐Salomon, A., & Karnoub, A. E. (2021) · npj Breast Cancer · doi:10.1038/s41523-021-00259-z · Cited by 13 · see citing works
USP40 promotes hepatocellular carcinoma progression through a YAP/USP40 positive feedback loop
Mo, H., Li, R., Yang, N., Han, J., Xiao, X., Zhang, Y., Xiao, Z., Jiao, L., Xu, Q., & Tu, K. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216832 · Cited by 13 · see citing works
PKCι and YAP1 are crucial in promoting pancreatic tumorigenesis
Wang, P., Wei, D., Zhang, H., Chen, J., Zhang, D., Ganapathy, S., Isakson, P., Chen, C., & Zhu, T. (2018) · Oncotarget · doi:10.18632/oncotarget.25127 · Cited by 12 · see citing works
Yorkie-Cactus (IκBα)-JNK axis promotes tumor growth and progression in Drosophila
Snigdha, K., Singh, A., & Kango-Singh, M. (2021) · Oncogene · doi:10.1038/s41388-021-01831-4 · Cited by 11 · see citing works
A Novel PHD2/VHL-mediated Regulation of YAP1 Contributes to VEGF Expression and Angiogenesis
Bora-Singhal, N., Saha, B., Mohankumar, D., Padmanabhan, J., Coppola, D., & Chellappan, S. (2022) · Cancer Research Communications · doi:10.1158/2767-9764.crc-21-0084 · Cited by 11 · see citing works
New insights in Hippo signalling alteration in human papillomavirus-related cancers
Olmedo‐Nieva, L., Muñoz-Bello, J. O., Manzo-Merino, J., & Lizano, M. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109815 · Cited by 10 · see citing works
Mohamed, A. D., Shah, N., Hettmer, S., Vargesson, N., & Wackerhage, H. (2018) · Scientific Reports · doi:10.1038/s41598-018-33852-7 · Cited by 10 · see citing works
A New Player in Neuroblastoma: YAP and Its Role in the Neuroblastoma Microenvironment
Shim, J., & Goldsmith, K. C. (2021) · Cancers · doi:10.3390/cancers13184650 · Cited by 10 · see citing works
MicroRNAs in Drosophila Cancer Models
Sander, M., & Herranz, H. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-23629-8_9 · Cited by 9 · see citing works
Groth, C., Vaid, P. M., Khatpe, A. S., Prashali, N., Ahiya, A., Andrējeva, D., Chakladar, M., Nagarkar, S., Paul, R., Kelkar, D. A., et al. (2020) · G3 Genes Genomes Genetics · doi:10.1534/g3.120.401545 · Cited by 8 · see citing works
Self-citationWang, S., Diao, S., Kim, H., Zou, J. Y., Li, K., & Koromilas, A. E. (2025) · Communications Biology · doi:10.1038/s42003-025-08740-2 · Cited by 8 · see citing works
RhoBTB Proteins Regulate the Hippo Pathway by Antagonizing Ubiquitination of LKB1
Nguyen, T., Ralbovska, A., & Kugler, J. (2020) · G3 Genes Genomes Genetics · doi:10.1534/g3.120.401038 · Cited by 7 · see citing works
SOCSs: important regulators of host cell susceptibility or resistance to viral infection
Zhang, X., Xia, H., Wang, Q., Cui, M., Zhang, C., Wang, Q., Liu, X., & Chen, K. (2023) · Zeitschrift für Naturforschung C · doi:10.1515/znc-2023-0024 · Cited by 7 · see citing works
Evidence of Cooperation between Hippo Pathway and RAS Mutation in Thyroid Carcinomas
Carneiro, T. N. R., Bim, L. V., Buzatto, V. C., Galdeno, V., Asprino, P. F., Lee, E. A., Galante, P. A. F., & Cerutti, J. M. (2021) · Cancers · doi:10.3390/cancers13102306 · Cited by 7 · see citing works
Concerted localization-resets precede YAP-dependent transcriptionPreprint
Ghosh, R. P., Franklin, J. M., Shi, Q., Reddick, M. P., & Liphardt, J. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/539049 · Cited by 7 · see citing works
Acinar Ductal Metaplasia: Yap Fills a Gap
Means, A. L., & Logsdon, C. D. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.07.022 · Cited by 6 · see citing works
Baghaei, K., Hosseinkhan, N., Aghdaei, H. A., & Zali, M. R. (2017) · Molecular BioSystems · doi:10.1039/c7mb00450h · Cited by 5 · see citing works
Yang, H., Li, Y., Li, X., Yan, Q.-M., Han, X.-Z., Cao, J., Sang, H.-P., & Li, J. (2023) · EXPERIMENTAL ANIMALS · doi:10.1538/expanim.23-0041 · Cited by 5 · see citing works
The RAS and YAP1 dance, who is leading?
Corbo, V., Ponz‐Sarvisé, M., & Tuveson, D. A. (2014) · The EMBO Journal · doi:10.15252/embj.201490014 · Cited by 5 · see citing works
Recent advances on Hippo-YAP pathway in skin diseases
Cai, X., Chen, K., Li, X., Zhang, K., Gu, J., Shen, C., Yu, B., & Huang, C. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1728064 · Cited by 4 · see citing works
Apollonio, M., Bellazzo, A., Franco, N., Lombardi, S., Senigagliesi, B., Casalis, L., Parisse, P., Thalhammer, A., Baj, G., Fania, R. D. F., et al. (2023) · Cancers · doi:10.3390/cancers15133379 · Cited by 4 · see citing works
Olatunde, D., & Benedetti, A. D. (2024) · Cancers · doi:10.3390/cancers16162918 · Cited by 4 · see citing works
- Authors
- Hong, X., Nguyen, H. T., Chen, Q., Zhang, R., Hagman, Z., Voorhoeve, P. M., & Cohen, S. M.
- Affiliations
- National University of Singapore (SG)
- Singapore-MIT Alliance for Research and Technology (SG)
- Stanford University (US)
- University of Copenhagen (DK)
- Corresponding author
- Cohen, Stephen M
- Venue
- The EMBO Journal
- Published
- 2014-09-01
- Volume
- 33
- Issue
- 21
- Pages
- 2447-2457
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC4283404
- OpenAlex
- W2153517086
- Cited by
- 121
- References
- 49
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 12 · 2022: 4 · 2021: 15 · 2020: 12 · 2019: 10 · 2018: 13 · 2017: 15 · 2016: 18 · 2015: 8 · 2014: 1
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The EMBO Journal (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion, cc-by)
- Funders
- NMRC (CBRG12nov010)
- Duke‐NUS Signature Research Program
- Ministry of Health (MOE2010‐T2‐2‐006)
- IMCB
- NovoNordisk Foundation Laureate Award
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- Ras signaling, Hippo signaling pathway, YAP, protein turnover, ubiquitin ligase, anchorage-independent growth, cell transformation, tumor suppressor, EGFR signaling, amphiregulin, positive feedback loop, oncogenic Ras
- MeSH terms
- Hippo Signaling Pathway, YAP-Signaling Proteins, Cell Transformation, Neoplastic, Humans, Phosphoproteins, Transcription Factors, Signal Transduction, Up-Regulation, Protein Serine-Threonine Kinases, ras Proteins, SKP Cullin F-Box Protein Ligases, beta-Transducin Repeat-Containing Proteins, Adaptor Proteins, Signal Transducing, Suppressor of Cytokine Signaling Proteins, Protein Stability, HEK293 Cells, ErbB Receptors
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