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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
The Tumor Suppressor Interferon Regulatory Factor 2 Binding Protein 2 Regulates Hippo Pathway in Liver Cancer by a
Xue Feng1, Tiantian Lu1, Jinhui Li1
1State 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.
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.
Insights
Interferon regulatory factor 2 binding protein 2 (IRF2BP2) suppresses liver cancer by inhibiting the Hippo pathway's YAP/TEAD complex. This discovery reveals a key feedback loop for organ-size control and cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- Cell Signaling
Background:
- The Hippo pathway is crucial for organ size regulation and preventing cancer.
- Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a known transcriptional corepressor.
- The role of IRF2BP2 in the Hippo pathway and liver cancer is not well understood.
Purpose of the Study:
- To investigate the clinical significance of IRF2BP2 in hepatocellular carcinogenesis.
- To elucidate the regulatory mechanism of IRF2BP2 within the Hippo pathway.
- To understand the biological function of IRF2BP2 in liver cancer.
Main Methods:
- Investigated IRF2BP2 as a direct target of the YAP/TEAD4 complex.
- Analyzed the feedback loop mechanism involving IRF2BP2 and YAP.
- Examined the effect of IRF2BP2 on vestigial-like family member 4 (VGLL4) stability and function.
- Assessed the impact of liver-specific IRF2BP2 overexpression on tumor formation.
Main Results:
- IRF2BP2 acts as a suppressor of hepatocellular carcinogenesis.
- IRF2BP2 inhibits YAP activity through a feedback loop, stabilizing VGLL4.
- Overexpression of IRF2BP2 in the liver prevents tumor formation caused by Hippo pathway inactivation.
Conclusions:
- IRF2BP2 plays a critical role in repressing liver cancer progression.
- A novel feedback loop involving IRF2BP2, YAP, and VGLL4 is identified.
- This feedback loop is important for Hippo pathway-mediated organ-size control and tumorigenesis.
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