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Yes-Associated Protein Up-regulates Jagged-1 and Activates the NOTCH Pathway in Human Hepatocellular Carcinoma
Open accessAbstract
Background & aims Cancer cells often lose contact inhibition to undergo anchorage-independent proliferation and become resistant to apoptosis by inactivating the Hippo signaling pathway, resulting in activation of the transcriptional co-activator yes-associated protein (YAP). However, the oncogenic mechanisms of YAP activity are unclear.Methods By using cross-species analysis of expression data, the Notch ligand Jagged-1 (Jag-1) was identified as a downstream target of YAP in hepatocytes and hepatocellular carcinoma (HCC) cells. We analyzed the functions of YAP in HCC cells via overexpression and RNA silencing experiments. We used transgenic mice that overexpressed a constitutively activated form of YAP (YAP(S127A)), and measured protein levels in HCC, colorectal and pancreatic tumor samples from patients.Results Human HCC cell lines and mouse hepatocytes that overexpress YAP(S127A) up-regulated Jag-1, leading to activation of the Notch pathway and increased proliferation. Induction of Jag-1, activation of Notch, and cell proliferation required binding of YAP to its transcriptional partner TEA domain family member 4 (TEAD4); TEAD4 binding required the Mst1/2 but not β-catenin signaling. Levels of YAP correlated with Jag-1 expression and Notch signaling in human tumor samples and correlated with shorter survival times of patients with HCC or colorectal cancer.Conclusions The transcriptional regulator YAP up-regulates Jag-1 to activate Notch signaling in HCC cells and mouse hepatocytes. YAP-dependent activity of Jag-1 and Notch correlate in human HCC and colorectal tumor samples with patient survival times, suggesting the use of YAP and Notch inhibitors as therapeutics for gastrointestinal cancer. Transcript profiling: microarray information was deposited at the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jxepvsumwosqkve&acc=GSE35004).
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“Despite the protective effects of IL-6, YAP-mediated Notch signaling activation contributed to tumor growth in human hepatocellular carcinoma and murine hepatocytes (Tschaharganeh et al., 2013”
From Targeting Interleukin-6 Signaling in Clinic (2019) · cites this paper as Tschaharganeh et al., 2013
Experimental — accuracy not yet measuredIn the citing paper
“Over the years, a number of inhibitors targeting YAP/TAZ-TEAD have been reported, including peptides such as super-TDU (173),437 and small molecules such as verteporfin (174) and MGH-CP1 (175).438–440”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [439]
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1 retracted
Wang, C., Qi, R., Li, N., Wang, Z., An, H., Zhang, Q., Yu, Y., & Cao, X. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.002105 · Cited by 90
RetractedZhao, 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 · cited 6×
“Mst1), occurs in 50 to 70% of HCCs.(3,5,11) Also, functional studies have revealed oncogenic properties for nuclear YAP.”
InfluentialTEAD 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 · cited 1×
“YAP regulates target gene transcription in tumor and non-malignantly transformed cells through interaction with different transcription factors including TEAD family members.(18) Our results demonstrate that YAP-dependent expression of Jag-1 strictly depends on the presence of TEAD4, while other known binding partners…”
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 · cited 9×
“To define the effector mechanisms mediating protumorigenic properties of YAP, expression profiles of human HuH-7 cells after YAP knockdown were compared with transcriptomic data of murine hepatocytes with inducible YAP expression (Figure 1A).(5) YAP-dependent expression of genes inversely regulated (including CTGF, CX…”
InfluentialLiu-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 · cited 1×
“Importantly, the increased luciferase activity of Jag-1 region 1 was inhibited in a dose-dependent manner when either YAP or TEAD4 plasmid transfection was paralleled by treatment with verteporfin, a drug, which disrupts the YAP-TEAD binding (Figure 4D).(19)”
The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells
Cordenonsi, M., Zanconato, F., Azzolin, L., Forcato, M., Rosato, A., Frasson, C., Inui, M., Montagner, M., Parenti, A. R., Poletti, A., et al. (2011) · Cell · doi:10.1016/j.cell.2011.09.048 · Cited by 1,381 · cited 1×
“Accumulating evidence supports the importance of the tumor-suppressive Hippo pathway and its mediator YAP in cancer.(1,3-7,12,23) Here, we demonstrate that overexpression of YAP exerts its tumor-supporting properties partly through TEAD4dependent Jag-1 expression and subsequent activation of the Notch pathway in gastr…”
YAP1 increases organ size and expands undifferentiated progenitor cells
Camargo, F. D., Gokhale, S., Johnnidis, J. B., Fu, D., Bell, G. W., Jaenisch, R., & Brummelkamp, T. R. (2007) · Current Biology · doi:10.1016/j.cub.2007.10.039 · Cited by 1,252 · cited 5×
“For this purpose, primary murine hepatocytes were isolated from 10 week old transgenic animals expressing YAP under negative control of the liver-specific LAP doxycycline transactivator domain.(8) Short-term administration of doxycycline and subsequent downregulation of YAP were followed by reduced expression of Jag-1…”
InfluentialThe Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal
Zhao, B., Tumaneng, K., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2303 · Cited by 1,205 · cited 1×
“Inactivation of the Hippo pathway leads to the nuclear translocation of YAP and subsequent interaction with several transcription factors including TEAD and SMAD family members, Runx2, or p73.(2)”
Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach
Zender, L., Spector, M. S., Xue, W., Flemming, P., Cordon-Cardo, C., Silke, J., Fan, S.-T., Luk, J. M., Wigler, M., Hannon, G. J., et al. (2006) · Cell · doi:10.1016/j.cell.2006.05.030 · Cited by 1,065 · cited 7×
“Although transcription factors are believed to be non- 21 druggable due to large and stable protein/DNA surface interactions, crystal structure analysis of the YAP/TEAD4 complex demonstrated that the proteins are connected mainly via two short helices, one in the C-terminal domain of TEAD4 and one in the N-terminal re…”
InfluentialClassification and prediction of survival in hepatocellular carcinoma by gene expression profiling
Lee, J., Chu, I., Heo, J., Calvisi, D. F., Sun, Z., Roskams, T., Durnez, A., Demetris, A. J., & Thorgeirsson, S. S. (2004) · Hepatology · doi:10.1002/hep.20375 · Cited by 942
Self-citation
Research works printed but not linked: 1
- Camargo, 2007, YAP1 increases organ size and expands undifferentiated progenitor cells, Curr Biol, 17, 2054, 10.1016/j.cub.2007.10.039 · DOI · Paper page
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Items 101–200 of 327
Weiler, S. M. E., Lutz, T., Bissinger, M., Sticht, C., Knaub, M., Gretz, N., Schirmacher, P., & Breuhahn, K. (2020) · Cancer Letters · doi:10.1016/j.canlet.2019.12.044 · Cited by 65
Self-citationMiR-506 suppresses proliferation of hepatoma cells through targeting YAP mRNA 3′UTR
Wang, Y., Cui, M., Sun, B., Liu, F.-B., Zhang, X., & Ye, L. (2014) · Acta Pharmacologica Sinica · doi:10.1038/aps.2014.59 · Cited by 60
SIRT1 in the Development and Treatment of Hepatocellular Carcinoma
Farcas, M. F., Andrei-Alexandru, G., Gulei, D., Ionescu, C., Irimie, A., Cătană, C.-S., & Berindan‐Neagoe, I. (2019) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00148 · Cited by 61
Zhou, X., Su, J., Feng, S., Wang, L., Yin, X., Yan, J., & Wang, Z. P. (2016) · Oncotarget · doi:10.18632/oncotarget.12596 · Cited by 59
Oncogenic Determination of a Broad Spectrum of Phenotypes of Hepatocyte-Derived Mouse Liver Tumors
Yamamoto, M., Bing, X., Watanabe, K., Ooshio, T., Fujii, K., Chen, X., Okada, Y., Abe, H., Taguchi, Y., Miyokawa, N., et al. (2017) · American Journal Of Pathology · doi:10.1016/j.ajpath.2017.07.022 · Cited by 62
“…by Fan et al. 23 Because activation of the Notch signaling pathway via stimulation by Jagged-1 has been re-ported in human HCC lacking ductular differentiation, 39 YAP-induced activation of the Notch signaling pathway may not be suf fi cient to induce cholangiocytic differentiation in liver tumors.”
BackgroundSelf-citationThe hippo pathway: A master regulator of liver metabolism, regeneration, and disease
Nguyen‐Lefebvre, A. T., Selzner, N., Wrana, J. L., & Bhat, M. (2021) · The FASEB Journal · doi:10.1096/fj.202002284rr · Cited by 58
Activation of signal transduction pathways during hepatic oncogenesis
Chung, W., Kim, M., de la Monte, S. M., Longato, L., Carlson, R. I., Slagle, B. L., Dong, X., & Wands, J. R. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.09.016 · Cited by 57
Jones, P., Kaiser, M., Ghaderi-Najafabadi, M., Koplev, S., Zhao, Y.-Q., Douglas, G., Kyriakou, T., Andrews, S., Rajmohan, R., Watkins, H., et al. (2018) · Arteriosclerosis, Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.310976 · Cited by 50
MicroRNA-506 inhibits gastric cancer proliferation and invasion by directly targeting Yap1
Deng, J., Wan, L., Xiang, X., Zhang, L., Yu, F., Chen, J., Miao, F., & Xiong, J. (2015) · Tumor Biology · doi:10.1007/s13277-015-3364-8 · Cited by 57
The dual functions of YAP-1 to promote and inhibit cell growth in human malignancy
Wang, H., Du, Y. C., Zhou, X. J., Liu, H., & Tang, S. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-013-9463-3 · Cited by 57
Hippo‐yap signaling in ocular development and disease
Lee, M., Goraya, N., Kim, S., & Cho, S. (2018) · Developmental Dynamics · doi:10.1002/dvdy.24628 · Cited by 55
“…for malignancies because it is up-regulated in a variety of tumors, including colon cancer, hepatocellular carcinoma, ovarian cancer (Cai and Xu, 2013; Rosenbluh et al., 2012; Tschaharganeh et al., 2013; Zhang et al., 2014), pancreatic adenocarcinoma, and uveal melanoma (UM) (Yu et al., 2014a).”
BackgroundThe Hippo Pathway Regulates Hematopoiesis in Drosophila melanogaster
Milton, C. C., Grusche, F., Degoutin, J. L., Yu, E., Dai, Q., Lai, E. C., & Harvey, K. F. (2014) · Current Biology · doi:10.1016/j.cub.2014.10.031 · Cited by 60
Jagged 1 is a major Notch ligand along cholangiocarcinoma development in mice and humans
Che, L., Fan, B., Pilo, M. G., Xu, Z., Liu, Y., Cigliano, A., Cossu, A., Palmieri, G., Pascale, R. M., Porcu, A., et al. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.73 · Cited by 56
Self-citationWei, D., Zhang, G., Zhu, Z. G., Zheng, Y., Yan, F., Pan, C.-X., Wang, Z., Li, X., Wang, F., Meng, P., et al. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00690 · Cited by 55
“Tschaharganeh et al. (2013) reported that overexpress YY1AP1 in hepatoma carcinoma cell leading the proliferation.”
Li, H., Li, Q.-Y., Jin, M.-J., Lu, C.-F., Mu, Z.-Y., Xu, W., Song, J., Zhang, Y., & Zhang, S. (2021) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-021-03604-8 · Cited by 55
“Through the luciferase reporter assay and ChIP, it was found that the interaction between YAP and TEAD4 directly binds to the JAG1 promoter in breast cancer cells to induce JAG1 expression, thereby up-regulating the JAG1 protein level (Tschaharganeh 2013).”
MethodInfluentialMiR-21-3p Promotes Hepatocellular Carcinoma Progression via SMAD7/YAP1 Regulation
Hong, Y., Ye, M., Wang, F., Fang, J., Wang, C., Luo, J., Liu, J., Liu, J., Liu, L., Zhao, Q., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.642030 · Cited by 56
Hu, G., Wu, L., Kuang, W., Chen, Y., Zhu, X.-G., Guo, H., & Lang, H. (2017) · Gene · doi:10.1016/j.gene.2017.02.006 · Cited by 53
Zhang, J., Wang, Y., Li, D., & Jing, S. (2013) · Tumor Biology · doi:10.1007/s13277-013-1053-z · Cited by 55
Yap and its subcellular localization have distinct compartment-specific roles in the developing lung
van Soldt, B. J., Qian, J., Li, J., Tang, N., Lü, J., & Cardoso, W. V. (2019) · Development · doi:10.1242/dev.175810 · Cited by 50
“…for Yap in ciliogenesis and in the regulation of Notch, a known determinant of cell fate decisions in the airway epithelium (de Lima et al., 2016; Grampa et al., 2016; Kim et al., 2015; Mahoney et al., 2014; Totaro et al., 2017; Tschaharganeh et al., 2013; Tu et al., 2018; Yimlamai et al., 2014).”
Zhu, Z., Xu, Y., Su, Q.-J., Du, J., Tan, X.-L., Tu, Y., Tan, J.-W., & Jiao, H.-B. (2013) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1897-y · Cited by 49
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
“…crosstalk have been reported in a variety of cell types, few reports in epithelia exist (de Lima, Bonnin, Birchmeier, & Duprez, 2016; Rayon et al., 2014; Slemmons et al., 2017; Tschaharganeh et al., 2013; Watanabe et al., 2017; Yimlamai et al., 2014; J. Yu, Poulton, Huang, & Deng, 2008).”
Thomann, S., Weiler, S. M. E., Marquard, S., Rose, F., Ball, C. R., Tóth, M., Wei, T., Sticht, C., Fritzsche, S., Roessler, S. K., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-0242 · Cited by 50
Self-citationZhang, H., Teng, X., Liu, Z., Zhang, L., & Liu, Z. (2015) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-015-0132-y · Cited by 48
“It also participates in the maintenance of tissue homeostasis by regulating cell proliferation, differentiation and apoptosis [46,47].”
BackgroundPrognostic Value of Yes-Associated Protein 1 (YAP1) in Various Cancers: A Meta-Analysis
Sun, Z., Xu, R., Li, X., Ren, W., Ou, C., Wang, Q., Zhang, H., Zhang, X., Ma, J., Wang, H., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135119 · Cited by 50
“Discussion Hippo signaling is an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, apoptosis, epithelial-mesenchymal transition, stem cell self renewal and cross talk with other pathways, such as TGF-β/SMAD [33], epidermal growth factor receptor signaling [34, 35], Hedgehog pa…”
Marquard, S., Thomann, S., Weiler, S. M. E., Bissinger, M., Lutz, T., Sticht, C., Tóth, M., Torre, C. D. L., Gretz, N., Straub, B. K., et al. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00634-6 · Cited by 48
Self-citationNOTCH target gene HES5 mediates oncogenic and tumor suppressive functions in hepatocarcinogenesis
Luiken, S., Fraas, A., Bieg, M., Sugiyanto, R. N., Goeppert, B. F., Singer, S., Ploeger, C., Warsow, G., Marquardt, J. U., Sticht, C., et al. (2020) · Oncogene · doi:10.1038/s41388-020-1198-3 · Cited by 49
Self-citationTargeting the Hippo pathway: Clinical implications and therapeutics
Ye, S., & Eisinger‐Mathason, T. S. K. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.11.025 · Cited by 46
LaQuaglia, M. P., Grijalva, J., Mueller, K. A., Pérez‐Atayde, A. R., Kim, H. B., Sadri‐Vakili, G., & Vakili, K. (2016) · Scientific Reports · doi:10.1038/srep30238 · Cited by 45
Wang, S., Cai, L., Zhang, F., Shang, X., Xiao, R., & Zhou, H. (2020) · Translational Oncology · doi:10.1016/j.tranon.2020.01.002 · Cited by 45
“In HCC, Notch signaling is activated and plays an oncogenic role [13, 14, 16].”
BackgroundChen, Y., Gianino, S. M., & Gutmann, D. H. (2015) · Genes & Development · doi:10.1101/gad.261677.115 · Cited by 45
“Several potential regulators of Jagged1 expression have been identified, including βcatenin, YAP, and TGFβ/Smad3 (Chen et al. 2010; Zhang et al. 2010; Tschaharganeh et al. 2013).”
BackgroundRole of the Hippo pathway in liver regeneration and repair: recent advances
Pibiri, M., & Simbula, G. (2022) · Inflammation and Regeneration · doi:10.1186/s41232-022-00235-5 · Cited by 47
“Several genes important for liver growth and regeneration, such as connective tissue growth factor 28 (Ctgf 28), Jagged 1 (Jag1) [53, 54] and Notch receptor 2 (Notch2), are direct targets of Hippo signaling.”
BackgroundHippo Pathway: An Emerging Regulator of Craniofacial and Dental Development
Wang, J., & Martin, J. F. (2017) · Journal of Dental Research · doi:10.1177/0022034517719886 · Cited by 43
“Recently, Hippo and Notch pathways have been shown to converge in the development of human hepatocellular carcinoma, the control of liver cell fate, and the regulation of cranial neural crest (CNC)–derived smooth muscle differentiation, primarily through Yap and Tead’s direct regulation of Notch ligand Jagged1 and rec…”
BackgroundLiu, D., Zhang, H., Cong, J., Cui, M., Ma, M., Zhang, F., Sun, H., & Chen, C. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29427 · Cited by 43
TGF-β2 silencing to target biliary-derived liver diseases
Dropmann, A., Dooley, S., Dewidar, B., Hammad, S., Dediulia, T., Werle, J., Hartwig, V., Ghafoory, S., Wölfl, S., Korhonen, H., et al. (2020) · Gut · doi:10.1136/gutjnl-2019-319091 · Cited by 43
Li, Y., Wang, S., Wei, X., Zhang, S., Song, Z., Chen, X., & Zhang, J. (2018) · Cancer Science · doi:10.1111/cas.13888 · Cited by 43
Self-citationMEK1 promotes YAP and their interaction is critical for tumorigenesis in liver cancer
Li, L., Wang, J., Zhang, Y., Zhang, Y., Ma, L., Weng, W., Qiao, Y., Xiao, W., Wang, H., Yu, W., et al. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.10.042 · Cited by 42
“Overexpression of YAP upregulates Jag-1, leading to activation of Notch pathway and increased proliferation [6].”
BackgroundCrouchet, É., Bandiera, S., Fujiwara, N., Li, S., Saghire, H. E., Fernández-Vaquero, M., Riedl, T., Sun, X., Hirschfield, H., Jühling, F., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25468-9 · Cited by 46
YAP/TAZ signalling in colorectal cancer: lessons from consensus molecular subtypes
Mouillet-Richard, S., & Laurent-Puig, P. (2020) · Cancers · doi:10.3390/cancers12113160 · Cited by 40
“Incidentally, JAGGED1 was subsequently identified as a YAP target gene [42].”
BackgroundEmerging role of Hippo signalling pathway in bladder cancer
Xia, J., Zeng, M., Zhu, H., Chen, X., Weng, Z., & Li, S. (2017) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13293 · Cited by 42
Self-citationTEAD4 as an Oncogene and a Mitochondrial Modulator
Hsu, S., Lin, C., Lin, Y., Collins, C. C., Chen, C., & Kung, H. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.890419 · Cited by 38
Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade
Jia, J., Qiao, Y., Pilo, M. G., Cigliano, A., Liu, X., Shao, Z., Calvisi, D. F., & Chen, X. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184068 · Cited by 39
Self-citationWang, L., Zhu, Z., Han, L., Zhao, L., Weng, J., Yang, H., Wu, S., Chen, K., Wu, L. L., & Chen, T. (2019) · Food & Function · doi:10.1039/c8fo02448k · Cited by 39
Role of the Notch signaling in cholangiocarcinoma
Cigliano, A., Wang, J., Chen, X., & Calvisi, D. F. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1310842 · Cited by 39
“Moreover, YAP levels were proven to correlate with Jag-1 expression and Notch signaling activation in human HCC and colorectal tumor samples, in which they were associated with shorter patients’ survival [78].”
BackgroundSelf-citationRegulation of Hippo signaling pathway in cancer: A MicroRNA perspective
Samji, P., Rajendran, M. K., Warrier, V. P., Ganesh, A., & Karunagaran, D. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109858 · Cited by 40
Engel-Pizcueta, C., & Pujades, C. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.711531 · Cited by 38
The biology of YAP in programmed cell death
Cheng, Y., Mao, M., & Lu, Y. (2022) · Biomarker Research · doi:10.1186/s40364-022-00365-5 · Cited by 42
“Hepatocellular carcinoma patients with a poor response to transarterial chemoembolization (TACE) had higher YAP protein levels than responsive patients, indicating Hepatocellular cancer YAP-TEAD Jag-1↑ Notch signaling Anti-Apoptosis [62] Breast cancer YAP-TEAD BCAR4↑ Hedgehog signaling Anti-Apoptosis [63] Hepatocellul…”
BackgroundTargeting Transcription Factors in Cancer: From “Undruggable” to “Druggable”
Tao, Z., & Wu, X. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2815-7_9 · Cited by 39
Wei, S., Wang, J., Oyinlade, O., Ma, D., Wang, S., Kratz, L. E., Lal, B., Xu, Q., Liu, S., Shah, S. R., et al. (2018) · Oncogene · doi:10.1038/s41388-018-0334-9 · Cited by 37
“In some tissues, YAP acts as an oncogene but in other tissues YAP functions as a tumor suppressor.35 In our system, we identified Notch pathway downstream of YAP, consistent with the work from Tschaharganeh.36 Since YAP promoter was not hypermethylated in IDH1R132H/WT cells when compared to control, the mechanism of Y…”
ResultInfluentialA Peculiar Mutation Spectrum Emerging from Young Peruvian Patients with Hepatocellular Carcinoma
Marchio, A., Bertani, S., Rojas, T. R., Doimi, F. D., Terris, B., Deharo, E., Dejean, A., Ruíz, E., & Pineau, P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114912 · Cited by 36
Hippo Cascade Controls Lineage Commitment of Liver Tumors in Mice and Humans
Zhang, S., Wang, J., Wang, H., Fan, L., Fan, B., Zeng, B., Tao, J., Li, X., Che, L., Cigliano, A., et al. (2018) · American Journal Of Pathology · doi:10.1016/j.ajpath.2017.12.017 · Cited by 35
Self-citationMolina, L. M., Zhu, J., Qin, L., Pradhan‐Sundd, T., Krutsenko, Y., Sayed, K., Jenkins, N. E. C., Vats, R., Bhushan, B., Ko, S., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109310 · Cited by 36
Zhang, S., Zhang, J., Evert, K., Li, X., Pin, L., Kiss, A., Schaff, Z., Ament, C. E., Zhang, Y., Serra, M., et al. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.03.011 · Cited by 35
Self-citationGarcía, B. G., & Baladrón, V. (2015) · Biology of the Cell · doi:10.1111/boc.201500029 · Cited by 35
“The JAGGED1 ligand is regulated by yes-associated protein, which is over-expressed in HCC, and correlates with the level of proliferation of the tumour (Tschaharganeh et al., 2013).”
BackgroundLi, Y., Zhang, X., Zheng, Q., Zhang, Y., Ma, Y., Zhu, C., Yang, L., Peng, X., Wang, Q., Wang, B., et al. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.05.021 · Cited by 35
RetractedNotch Signaling and Liver Cancer
Kawaguchi, K., & Kaneko, S. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-55031-8_6 · Cited by 37
Weng, H., Wang, X., Li, M., Wu, X., Wang, Z., Wu, W., Zhang, Z., Zhang, Y., Zhao, S., Liu, S., et al. (2015) · Cancer Biology & Therapy · doi:10.1080/15384047.2015.1070994 · Cited by 33
Mechanotransduction and Cytoskeleton Remodeling Shaping YAP1 in Gastric Tumorigenesis
Zhang, J., Zhou, Y., Tang, P. M., Cheng, A. S. L., Yu, J. Q., To, K. F., & Kang, W. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071576 · Cited by 32
“YAP1 upregulates both ligand [53] and receptor [54] of Notch signaling pathway from the transcriptional level.”
BackgroundThomann, S., Weiler, S. M. E., Wei, T., Sticht, C., Torre, C. D. L., Tóth, M., Rose, F., Tang, Y., Ritz, T., Ball, C. R., et al. (2021) · Liver International · doi:10.1111/liv.15048 · Cited by 35
Self-citationZeng, S., Jian-hong, X., Zeng, Q.-Y., Dai, S., Wang, Y., Wan, X.-M., & Liu, J. C. H. (2021) · PubMed Central · doi:10.22074/cellj.2021.7010 · Cited by 32
“of Jag1 and Notch were also reported to correlate with survival times in human HCC and colorectal tumor samples (19).”
BackgroundAdvances in Liver Regeneration: Revisiting Hepatic Stem/Progenitor Cells and Their Origin
Sadri, A.-R., Jeschke, M. G., & Amini‐Nik, S. (2015) · Stem Cells International · doi:10.1155/2016/7920897 · Cited by 33
Bailey, D. D., Zhang, Y., van Soldt, B. J., Jiang, M. Z., Suresh, S., Nakagawa, H., Rustgi, A. K., Aceves, S. S., Cardoso, W. V., & Que, J. (2019) · Development · doi:10.1242/dev.178855 · Cited by 31
“…identified Notch signaling as an important pathway in the differentiation of EPCs (Zhang et al., 2018) and several studies have demonstrated that Yap directly activates Notch signaling by increasing the expression of Notch ligands and receptors (Tschaharganeh et al., 2013; Yimlamai et al., 2014).”
Sun, Y., Tang, L., Kan, X., Tan, L., Song, C., Qiu, X., Liao, Y., Nair, V., Ding, C., Liu, X., et al. (2024) · Journal of Virology · doi:10.1128/jvi.01897-23 · Cited by 30
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 33
Wang, F., Li, S., Kong, L., Feng, K., Zuo, R., Zhang, H., Yu, Y., Zhang, K., Cao, Y., Chai, Y., et al. (2024) · Advanced Science · doi:10.1002/advs.202309133 · Cited by 30
MicroRNA-345 inhibits hepatocellular carcinoma metastasis by inhibiting YAP1
Zhang, H., Liu, H., & Bi, H. (2017) · Oncology Reports · doi:10.3892/or.2017.5772 · Cited by 29
“Among numerous predicted downstream targets, YAP1 is an attractive one since YAP1 is a well-known oncogenic protein in HCC (15,16).”
RetractedLü, T., Sun, L., & Zhu, X. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.06.031 · Cited by 29
Liu, J., Zhao, X., Wang, K., Zhang, X., Yu, Y., Lv, Y., Zhang, S., Zhang, L., Guo, Y., Li, Y., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1674-2 · Cited by 31
Nguyen, Q. P., Anders, R. A., Alpini, G. D., & Bai, H. (2015) · Digestive and Liver Disease · doi:10.1016/j.dld.2015.05.011 · Cited by 32
“YAP activation n mouse livers increases mRNA levels of several Notch pathway omponents including Notch1/2, Jag1 (Jagged 1), Hes1 (hes family HLH transcription factor 1) and Sox9 (sex determining region Y-box ) [23,24], among which Notch2 is a direct target of YAP [24].”
BackgroundTryndyak, V., de Conti, A., Doerge, D. R., Olson, G. R., Beland, F. A., & Pogribny, I. P. (2016) · Archives of Toxicology · doi:10.1007/s00204-016-1786-8 · Cited by 29
Li, X., Cai, H., Wang, X., Ao, L., Guo, Y., He, J., Gu, Y., Qi, L., Guan, Q., Lin, X., et al. (2017) · Briefings in Bioinformatics · doi:10.1093/bib/bbx135 · Cited by 29
Liu, C., Cheng, X., Chen, J., Wang, Y., Wu, X., Tian, R. L., Liu, B., Ding, X., Sun, Q., & Gong, W. (2019) · Theranostics · doi:10.7150/thno.33370 · Cited by 28
“In tumor research models, the YAP/TAZ signaling pathway interacts with the Notch signaling pathway, which is a functional target of YAP/TAZ [25-27].”
BackgroundLee, K. B., Lee, K.-B., Jung, H. Y., Yi, N., Lee, K., Suh, K., & Jang, J. (2017) · BMC Cancer · doi:10.1186/s12885-017-3431-1 · Cited by 28
Zhang, J., Pin, L., Tao, J., Wang, P., Zhang, Y., Song, X., Che, L., Sumazin, P., Ribback, S., Kiss, A., et al. (2019) · American Journal Of Pathology · doi:10.1016/j.ajpath.2019.01.016 · Cited by 28
“In previous studies, TEAD4 was established as the main TEAD isoform in hepatocellular carcinoma development.(41,42) According to these data, it is tempting to speculate that TEAD4 might represent the key TEAD protein along liver”
BackgroundSelf-citationChen, B., & Jin, W. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1200061 · Cited by 29
Li, S., Hao, L., Li, N., Hu, X., Yan, H., Dai, E., & Shi, X. (2024) · International Journal of Oncology · doi:10.3892/ijo.2024.5676 · Cited by 36
“These results show that YAP1 and Notch inhibitors can be used as therapeutics for gastrointes‑ tinal cancers (147).”
BackgroundNotch Signaling Regulation in HCC: From Hepatitis Virus to Non-Coding RNAs
Giovannini, C., Fornari, F., Piscaglia, F., & Gramantieri, L. (2021) · Cells · doi:10.3390/cells10030521 · Cited by 27
“To assess whether in vitro findings reflected the biology of human HCC, YAP, Jagged1 and Notch1 expression were analyzed by immunohistochemistry and a positive correlation was found among these proteins and their upregulation associated with a poor prognosis [62].”
BackgroundJagged1 DNA Copy Number Variation Is Associated with Poor Outcome in Liver Cancer
Kawaguchi, K., Honda, M., Yamashita, T., Okada, H., Shirasaki, T., Nishikawa, M., Nio, K., Arai, K., Sakai, Y., Yamashita, T., et al. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2016.04.011 · Cited by 29
“34 However, recent cancer research has revealed that copy number changes in speci fi c genes are associated with carcinogenesis or the aggressiveness of the cancer and correlate with patient survival.”
BackgroundPorcheri, C., & Mitsiadis, T. A. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-55031-8_7 · Cited by 29
Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview
Brivio, S., Cadamuro, M., Fabris, L., & Strazzabosco, M. (2017) · Gene Expression · doi:10.3727/105221617x15088670121925 · Cited by 26
Role of YAP1 Signaling in Biliary Development, Repair, and Disease
Molina, L. M., Nejak‐Bowen, K. N., & Monga, S. P. (2022) · Seminars in Liver Disease · doi:10.1055/s-0041-1742277 · Cited by 29
Wang, L., Wan, X.-Y., Liu, C.-Q., & Zheng, F.-M. (2022) · Molecular Medicine · doi:10.1186/s10020-022-00480-x · Cited by 23
de Conti, A., Tryndyak, V., Doerge, D. R., Beland, F. A., & Pogribny, I. P. (2016) · Food and Chemical Toxicology · doi:10.1016/j.fct.2016.06.027 · Cited by 24
YAP and TAZ, the conductors that orchestrate eye development, homeostasis, and disease
Zhu, J., Lin, S., & Ye, J. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26870 · Cited by 23
Notch signalling pathway in development of cholangiocarcinoma
Rauff, B., Malik, A., Bhatti, Y. A., Chudhary, S. A., Qadri, I., & Rafiq, S. M. (2020) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v12.i9.957 · Cited by 26
Hepatic adaptation to chronic metabolic stress primes tumorigenesis
Tzouanas, C. N., Shay, J. E. S., Sherman, M. S., Rubin, A. J., Mead, B. E., Dao, T. T., Tao, J., Lehrich, B. M., Eng, G. M., Patterson-Fortin, J., et al. (2025) · Cell · doi:10.1016/j.cell.2025.11.031 · Cited by 32
Kitagawa, K., Moriya, K., Kaji, K., Saikawa, S., Sato, S., Nishimura, N., Namisaki, T., Akahane, T., Mitoro, A., & Yoshiji, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207588 · Cited by 23
“Several lines of experimental evidence [23,24,30] also demonstrated the close relationship of YAP with chemoresistance in HCC.”
BackgroundPan-cancer analysis, cell and animal experiments revealing TEAD4 as a tumor promoter in ccRCC
Li, F., Feng, Y., Jiang, Q., Zhang, J., Wu, F., Li, Q., Jing, X., Wang, X., & Huang, C. Y. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120327 · Cited by 23
Xu, F., Wang, Y., Chang, J.-J., Du, S., Diao, L., Jiang, N., Wang, H., Ma, D., & Zhang, J. (2013) · Biochemical Journal · doi:10.1042/bj20130986 · Cited by 23
Signalling pathways and transcriptional regulators orchestrating liver development and cancer
Campbell, S. A., Stephan, T. L., Lotto, J., Cullum, R., Drissler, S., & Hoodless, P. A. (2021) · Development · doi:10.1242/dev.199814 · Cited by 22
The Hippo pathway: Horizons for innovative treatments of peripheral nerve diseases
Feltri, M. L., Weaver, M. R., Belin, S., & Poitelon, Y. (2021) · Journal of the Peripheral Nervous System · doi:10.1111/jns.12431 · Cited by 23
Hepatitis B x (HBx) as a Component of a Functional Cure for Chronic Hepatitis B
Feitelson, M. A., Arzumanyan, A. L., Spector, I., & Medhat, A. (2022) · Biomedicines · doi:10.3390/biomedicines10092210 · Cited by 26
YAP1 is essential for malignant mesothelioma tumor maintenance
Calvet, L., Dos-Santos, O., Spanakis, E., Jean‐Baptiste, V., Bail, J.-C. L., Buzy, A., Paul, P., Henry, C., Valence, S., Dib, C., et al. (2022) · BMC Cancer · doi:10.1186/s12885-022-09686-y · Cited by 20
Han, S., Lim, J. Y., Cho, K., Lee, H. W., Park, J. Y., Ro, S. W., Kim, K. S., Seo, H. R., & Kim, D. Y. (2022) · Cancers · doi:10.3390/cancers14112733 · Cited by 20
Nakano, Y., Nakao, S., Sueoka, M., Kasahara, D., Tanno, Y., Sumiyoshi, H., Itoh, T., Miyajima, A., Hozumi, K., & Inagaki, Y. (2022) · Communications Biology · doi:10.1038/s42003-022-03013-8 · Cited by 21
YAP/TAZ affects the development of pulmonary fibrosis by regulating multiple signaling pathways
Zhu, T., Ma, Z., Wang, H., Jia, X., Wu, Y., Fu, L., Li, Z., Zhang, C., & Yu, G. (2020) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-020-03866-9 · Cited by 20
Xu, M., Wang, J., Xu, Z., Li, R., Wang, P., Shang, R., Cigliano, A., Ribback, S., Solinas, A., Pes, G. M., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-3750 · Cited by 20
Self-citationEl-Meguid, M. A., Dawood, R. M., Mokhles, M. A., & Awady, M. K. E. (2018) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2018.0045 · Cited by 18
Tao, L., Chen, X., Zheng, Y., Wu, Y., Jiang, X., You, M., Li, S., & Hu, F. (2021) · Molecules · doi:10.3390/molecules26092803 · Cited by 18
“Furthermore, the Hippo pathway has been implied to interact with multiple pathways including mTOR [72], Wnt [73], Hedgehog [74], and Notch [75], to regulate the proliferation of cancer cells.”
BackgroundSelf-citationRole of Hippo pathway dysregulation from gastrointestinal premalignant lesions to cancer
Schiavoni, G., Messina, B., Scalera, S., Memeo, L., Colarossi, C., Mare, M., Blandino, G., Ciliberto, G., Bon, G., & Maugeri‐Saccà, M. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05027-8 · Cited by 20
“YAP/TAZ control HCC progression through multiple mechanisms including crosstalk with protumorigenic pathways [41–45] and interaction with metabolic processes [46, 47] and stemness factors [48, 49].”
BackgroundSerum CD166: A novel hepatocellular carcinoma tumor marker
Ma, L., Lin, J., Qiao, Y., Weng, W., Liu, W., Wang, J., & Sun, F. (2015) · Clinica Chimica Acta · doi:10.1016/j.cca.2014.12.034 · Cited by 18
“The transmembrane protein Jag-1 is a downstream target of YAP in liver cancer cells [19], but serum Jag-1 for the diagnosis of liver cancer has not been identified.”
Background
Metadata
- Authors
- Tschaharganeh, D. F., Chen, X., Latzko, P., Malz, M., Gaida, M. M., Felix, K., Ladu, S., Singer, S., Pinna, F., Gretz, N., Sticht, C., Tomasi, M. L., Delogu, S., Evert, M., Fan, B., Ribback, S., Jiang, L., Brozzetti, S., Bergmann, F., Dombrowski, F., Schirmacher, P., Calvisi, D. F., & Breuhahn, K.
- Affiliations
- University Hospital Heidelberg (DE)
- University of California, San Francisco (US)
- University of Chieti-Pescara (IT)
- Medizinische Fakultät Mannheim (DE)
- University of Southern California (US)
- Universität Greifswald (DE)
- Sapienza University of Rome (IT)
- Corresponding author
- Breuhahn, Kai
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 144
- Issue
- 7
- Pages
- 1530-1542.e12
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC3665638
- OpenAlex
- W2060323466
- Cited by
- 326
- References
- 47
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 16 · 2023: 19 · 2022: 26 · 2021: 29 · 2020: 35 · 2019: 26 · 2018: 26 · 2017: 25 · 2016: 28 · 2015: 35 · 2014: 28 · 2013: 8
- FWCI
- 19.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- YAP, Jagged1, Notch signaling, hepatocellular carcinoma, TEAD4, MST1/2, Hippo signaling pathway, colorectal cancer, pancreatic cancer, cell proliferation, patient survival, transcriptional coactivator, therapeutic target
- MeSH terms
- Serrate-Jagged Proteins, Jagged-1 Protein, YAP-Signaling Proteins, TEA Domain Transcription Factors, Animals, Calcium-Binding Proteins, DNA-Binding Proteins, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Membrane Proteins, Muscle Proteins, Phosphoproteins, Transcription Factors, Up-Regulation, Gene Expression Regulation, Neoplastic, Cell Cycle Proteins, Hepatocytes, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice, Receptors, Notch
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