Cited by 24Hippo pathway signaling and YAP/TAZLiver physiology and pathologyCancer-related molecular mechanisms research

YAP transcriptionally regulates ErbB2 to promote liver cell proliferation

Wang, Evan Y., Cheng, Jung-Chien, Thakur, Avinash, Yi, Yuyin, Tsai, Shu-Huei, Hoodless, Pamela A.·2018·Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Abstract

The Hippo signaling pathway is implicated in regulation of liver size and dysregulation of this pathway contributes to tumorigenesis. The transcriptional targets and downstream pathways of the Hippo pathway effector YAP that contribute to liver growth have yet to be well-characterized. We examined the liver transcriptome in response to YAP overexpression and identify the ErbB signaling pathway as a mediator of cell growth downstream of YAP. ErbB2 is transcriptionally regulated by YAP in both the mouse liver and in HepG2 human hepatoma cells. Knockdown of YAP or pharmacological inhibition with verteporfin reduced ERBB2 levels in HepG2 cells. Analysis of ChIP-seq data revealed enrichment of the transcription factor TEAD4 at the ERBB2 promoter. Using luciferase reporter and chromatin immunoprecipitation assays, we show that YAP and TEAD4 directly bind to and activate a regulatory element in the ErbB2 promoter in both the mouse liver and HepG2 cells. Functionally, knockdown of YAP reduced EGF-induced ERBB2-mediated HepG2 cell proliferation and PI3K/AKT activation. Our findings highlight a mechanism by which YAP exerts its effects on liver cell proliferation through the ErbB signaling pathway by directly regulating the transcription of ErbB2.

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Crossref · 10.1016/j.bbagrm.2018.07.004

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Authors
Wang, E. Y., Cheng, J.-C., Thakur, A., Yi, Y., Tsai, S.-H., & Hoodless, P. A.
Affiliations
BC Cancer Agency (CA)
Corresponding author
Hoodless, Pamela A.
Venue
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Publisher
Elsevier BV
Published
2018-09
Volume
1861
Issue
9
Pages
854-863
ISSN
1874-9399 (ISSN-L)
OpenAlex
W2884014489
Cited by
24
References
59
Citations by year
2026: 1 · 2025: 3 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 2 · 2019: 1
FWCI
1.29
Type
journal article
Language
en
Open access
closed
Locations
  • Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Michael Smith Health Research BC
  • Cancer Research Society (21466)
  • Canadian Institutes of Health Research (FRN-259575, PJT-153006)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
YAP, ERBB2, Hippo signaling pathway, liver cell proliferation, TEAD4, transcriptional regulation, EGF signaling, PI3K/Akt, hepatocellular carcinoma, liver growth, verteporfin

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