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RUNX3 is a novel negative regulator of oncogenic TEAD-YAP complex in gastric cancer

Y Qiao1, S J Lin2, Y Chen1

  • 1Cancer Science Institute of Singapore, National University of Singapore, Singapore.

Oncogene
|September 15, 2015
PubMed

Insights

Runt-related transcription factor 3 (RUNX3) suppresses tumors by inhibiting the TEAD-YAP complex, a key driver of cancer cell proliferation. This interaction is crucial for its tumor suppressor function in gastric cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Runt-related transcription factor 3 (RUNX3) is a known tumor suppressor frequently inactivated in gastric cancer.
  • The TEAD-YAP complex is a potent regulator of proliferative genes and is hyperactivated in various cancers, including liver and breast cancer.

Purpose of the Study:

  • To elucidate a novel mechanism of RUNX3 tumor suppressor activity involving the TEAD-YAP complex in gastric cancer.
  • To investigate the role of TEAD-YAP complex hyperactivation in gastric carcinogenesis and its correlation with patient survival.

Main Methods:

  • Investigated the physical interaction between RUNX3 and the TEAD-YAP complex using molecular biology techniques.
  • Assessed the impact of RUNX3-TEAD interaction on TEAD DNA-binding ability and downstream signaling.
  • Analyzed RUNX3 mutations, specifically R122C, for their effect on RUNX3-TEAD interaction.

Main Results:

  • The TEAD-YAP complex exhibits strong oncogenic activity in gastric epithelial cells and its increased expression correlates with poorer patient survival.
  • RUNX3 directly binds to the N-terminal region of TEAD, reducing its DNA-binding ability and attenuating TEAD-YAP signaling.
  • A known gastric cancer mutation (RUNX3 R122C) impairs the interaction between RUNX3 and TEAD.

Conclusions:

  • RUNX3 functions as a tumor suppressor in gastric carcinogenesis by negatively regulating the oncogenic TEAD-YAP complex.
  • Targeting the RUNX3-TEAD interaction could represent a novel therapeutic strategy for gastric cancer.

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