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STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling

Dong-E Tang1, Yong Dai1, Lie-Wen Lin1

  • 1Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern, University of Science and Technology, Shenzhen People's Hospital, Shenzhen, China.

Cancer Science
|August 9, 2019
PubMed

Insights

The E3 ubiquitin ligase STUB1 targets YAP1 for degradation, inhibiting cancer cell survival. Lower STUB1 levels correlate with higher YAP1, impacting gastric cancer progression and chemosensitivity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Yes-associated protein (YAP) is crucial for organ size and tumorigenesis.
  • YAP1 activation promotes cancer cell survival and chemoresistance.
  • The mechanism of YAP1 upregulation in cancer remains largely unknown.

Purpose of the Study:

  • To elucidate the molecular mechanism regulating YAP1 levels in cancer.
  • To investigate the role of E3 ubiquitin ligases in YAP1 stability.
  • To explore STUB1 as a potential therapeutic target in gastric cancer.

Main Methods:

  • Western blotting to assess protein levels of YAP1 and STUB1.
  • Ubiquitination assays to identify YAP1 ubiquitination sites.
  • Immunoprecipitation to confirm STUB1-YAP1 interaction.
  • Analysis of human gastric cancer cell lines and patient samples.

Main Results:

  • STUB1 directly ubiquitinates and destabilizes YAP1.
  • STUB1-mediated ubiquitination occurs at the K280 site via K48-linked polyubiquitination.
  • Low STUB1 expression correlates with high YAP1 levels in gastric cancer.
  • STUB1 promotes YAP1 turnover, enhancing cellular chemosensitivity.

Conclusions:

  • STUB1-mediated YAP1 degradation is a key regulatory mechanism in gastric cancer.
  • This pathway impacts cancer cell survival and response to chemotherapy.
  • Targeting STUB1-YAP1 interaction offers a potential therapeutic strategy for gastric cancer.
Keywords:
STUB1YAP1chemoresistancegastric cancerubiquitination

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