Journal
HEPATOLOGY
Volume 71, Issue 6, Pages 1988-2004Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1002/hep.30961
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Funding
- National Natural Science Foundation of China [31530043, 31625017]
- National Key Research and Development Program of China [2017YFA0103601]
- Strategic Priority Research Program of Chinese Academy of Sciences [XDB19000000]
- Shanghai Leading Talents Program
- Science and Technology Commission of Shanghai Municipality [19ZR1466300]
- China Postdoctoral Science Foundation [2017M621556, BX201700264]
- Youth Innovation Promotion Association CAS
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Background and Aims The conserved Hippo pathway regulates organ size, tissue homeostasis, and tumorigenesis. Interferon regulatory factor 2 binding protein 2 (IRF2BP2) was originally identified as a transcriptional corepressor. However, the association between IRF2BP2 and the Hippo pathway remains largely unknown. In addition, the biological function and regulation mechanism of IRF2BP2 in liver cancer are poorly understood. Approach and Results In this study, we uncovered the clinical significance of IRF2BP2 in suppressing hepatocellular carcinogenesis. We showed that IRF2BP2, a direct target repressed by the Yes-associated protein (YAP)/TEA domain transcription factor 4 (TEAD4) transcriptional complex, inhibited YAP activity through a feedback loop. IRF2BP2 stabilized vestigial-like family member 4 (VGLL4) and further enhanced VGLL4's inhibitory function on YAP. Moreover, liver-specific IRF2BP2 overexpression suppressed tumor formation induced by Hippo pathway inactivation. Conclusions These results revealed the important role of IRF2BP2 in repressing liver cancer progression and highlighted a feedback loop underlying the Hippo pathway in organ-size control and tumorigenesis.
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