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.

Biology Direct
|January 1, 2024
PubMed

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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