2. Academic Validation
  3. The Tumor Suppressor Interferon Regulatory Factor 2 Binding Protein 2 Regulates Hippo Pathway in Liver Cancer by a Feedback Loop in Mice

The Tumor Suppressor Interferon Regulatory Factor 2 Binding Protein 2 Regulates Hippo Pathway in Liver Cancer by a Feedback Loop in Mice

  • Hepatology. 2020 Jun;71(6):1988-2004. doi: 10.1002/hep.30961.
Xue Feng 1,  Tiantian Lu 1,  Jinhui Li 1,  Ruizeng Yang 1,  Liqiao Hu 2,  Yi Ye 3,  Feifei Mao 4,  Lingli He 1,  Jinjin Xu 1,  Zuoyun Wang 1,  Yingbin Liu 5,  Yonglong Zhang 1,  Hongbin Ji 1 3,  Yun Zhao 1 3,  Shuqun Cheng 4,  Wei Tian 2,  Lei Zhang 1 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • 2 Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
  • 3 School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • 4 Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
  • 5 Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PMID: 31538665 DOI: 10.1002/hep.30961
Abstract

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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