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Updated: Jul 6, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
GPR137 inactivates Hippo signaling to promote gastric cancer cell malignancy
Lin Li1,2, Jinlong Tang3, Bin Cao4
1National Clinical Research Center for Child Health, The Children's Hospital, Zhejiang University School of Medicine, No. 3333, Binsheng Road, Hangzhou, 310052, People's Republic of China.
Abstract:
As the fifth most common cancer in the world, gastric cancer (GC) ranks as the third major cause of cancer-related death globally. Although surgical resection and chemotherapy still remains the mainstay of potentially curative treatment for GC, chemotherapy resistance and adverse side effects limit their clinical applications. Thus, further investigation of the mechanisms of carcinogenesis in GC and discovery of novel biomarkers is of great concern. We herein report that the elevated expression of GPR137 is correlated with GC. Overexpression of GPR137 potentiates human gastric cancer AGS cell malignancy, including proliferation, migration, invasion, colony formation and xenograft growth in nude mice in vivo, whereas knockout of GPR137 by CRISPR/Cas9 gene editing exerts the opposite effects. Mechanistically, GPR137 could bind to MST, the upstream kinases in Hippo pathway, which disrupts the association of MST with LATS, subsequently activating the transcriptional co-activators, YAP and TAZ, and thereby triggering the target transcription and the alterations in GC cell biological actions consequently. Therefore, our findings may provide with the evidence of developing a potentially novel treatment method with specific target for GC.
Insights
Elevated GPR137 expression promotes gastric cancer (GC) malignancy. Targeting GPR137 may offer a novel therapeutic strategy for this common cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric cancer (GC) is a leading cause of cancer death worldwide.
- Current treatments like chemotherapy face limitations due to resistance and side effects.
- Identifying novel GC biomarkers and therapeutic targets is crucial.
Purpose of the Study:
- To investigate the role of GPR137 in gastric cancer development and progression.
- To explore the underlying molecular mechanisms of GPR137 in GC.
- To assess the therapeutic potential of targeting GPR137.
Main Methods:
- Correlation analysis of GPR137 expression with GC.
- Overexpression and knockout (CRISPR/Cas9) studies in human gastric cancer AGS cells.
- In vivo xenograft assays in nude mice.
- Mechanistic studies involving Hippo pathway components (MST, LATS, YAP, TAZ).
Main Results:
- Elevated GPR137 expression is correlated with gastric cancer.
- GPR137 overexpression enhances GC cell malignancy (proliferation, migration, invasion, colony formation, in vivo growth).
- GPR137 knockout inhibits these malignant phenotypes.
- GPR137 interacts with MST, disrupting MST-LATS association, activating YAP/TAZ, and promoting GC progression.
Conclusions:
- GPR137 plays a significant role in promoting gastric cancer progression.
- GPR137 acts via the Hippo signaling pathway by modulating MST/LATS/YAP/TAZ interactions.
- GPR137 represents a potential novel therapeutic target for gastric cancer treatment.
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