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Tensin-4-dependent MET stabilization is essential for survival and proliferation in carcinoma cells

Ghaffar Muharram1, Pranshu Sahgal1, Taina Korpela2

  • 1Turku Centre for Biotechnology, University of Turku, Turku, 20520, Finland; VTT Technical Research Centre of Finland, Turku, 20521, Finland.

Developmental Cell
|May 13, 2014
PubMed

Insights

Tensin-4 (TNS4) stabilizes MET, a key driver in many cancers. Disrupting this interaction leads to MET degradation and cancer cell death, highlighting TNS4 as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Aberrant MET tyrosine kinase receptor signaling drives cancer growth and promotes cancer cell dependency on MET.
  • Tensin-4 (TNS4) is implicated as an oncogene, but its precise role in cancer progression remains unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which Tensin-4 (TNS4) contributes to cancer, focusing on its interaction with the MET receptor.

Main Methods:

  • Investigated the interaction between TNS4 and phosphorylated MET using biochemical assays.
  • Assessed the impact of TNS4-MET interaction on MET protein stability, cell survival, proliferation, and migration.
  • Examined the effects of TNS4 loss or disrupted interaction on MET trafficking and degradation.
  • Correlated MET and TNS4 expression in human colon and ovarian carcinoma tissues.

Main Results:

  • TNS4 directly binds to phosphorylated MET via its SH2 domain, enhancing MET protein stability and promoting cell survival, proliferation, and migration.
  • TNS4 also stabilizes β1-integrin.
  • Disruption of the TNS4-MET interaction induces MET lysosomal trafficking, increased degradation, and subsequent death of MET-addicted cancer cells.
  • A significant correlation between MET and TNS4 expression was observed in human colon and ovarian carcinomas.

Conclusions:

  • TNS4 plays a critical role in maintaining MET stability and oncogenic signaling in cancer.
  • The TNS4-MET interaction represents a potential therapeutic vulnerability in MET-dependent cancers.

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