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Updated: Jul 10, 2025
07:16
Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
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p120 RasGAP and ZO-2 are essential for Hippo signaling and tumor-suppressor function mediated by p190A RhoGAP
Hanyue Ouyang1, Shuang Wu2, Wangji Li3
1GI Cell Biology Laboratory, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, P.R. China.
Cell Reports
|November 23, 2023
Summary
ARHGAP35 (p190A) acts as a tumor suppressor by activating the Hippo pathway. Its interaction with RasGAP and ZO-2 is crucial for tumor suppression and cell proliferation control, impacting patient survival.
Area of Science:
- Molecular Biology
- Cancer Biology
- Cell Signaling
Background:
- ARHGAP35 encodes p190A RhoGAP (p190A), a known tumor suppressor.
- p190A activates the Hippo pathway and was initially identified through binding to p120 RasGAP (RasGAP).
Purpose of the Study:
- To investigate the interaction of p190A with ZO-2 and its dependence on RasGAP.
- To elucidate the role of RasGAP and ZO-2 in p190A-mediated tumor suppression.
Main Methods:
- Co-immunoprecipitation assays to study protein interactions.
- Functional assays to assess Hippo pathway activation, cell proliferation, and epithelial-mesenchymal transition.
- Analysis of patient survival data based on gene expression levels.
Main Results:
- p190A interaction with ZO-2 is dependent on RasGAP.
- Both RasGAP and ZO-2 are essential for p190A to activate LATS kinases, induce MET, promote contact inhibition, and suppress tumors.
- RasGAP and ZO-2 are required for p190A's transcriptional modulation.
- Low ARHGAP35 expression correlates with shorter survival in patients with high TJP2 (ZO-2) transcript levels.
Conclusions:
- A novel tumor suppressor interactome for p190A involving ZO-2 and RasGAP is defined.
- RasGAP is essential for p190A to activate LATS kinases, independent of its canonical Ras signaling role.
- The findings highlight the clinical relevance of the p190A-RasGAP-ZO-2 axis in cancer progression and patient outcomes.
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