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A cross-talk between oncogenic Ras and tumor suppressor PTEN through FAK Tyr861 phosphorylation in NIH/3T3 mouse

Young Yil Bahk1, Ick-Hyun Cho, Tong Soo Kim

  • 1Protein Network Research Center, Yonsei University, 134, Shinchon-Dong, Seodeamoon-Gu, Seoul 120-749, Republic of Korea. bahk12@empal.com

Biochemical and Biophysical Research Communications
|November 13, 2008
PubMed

Insights

Oncogenic Ras suppresses PTEN, a tumor suppressor, through the Raf-1/Erk/MEK pathway. PTEN

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • Ras proteins are potent oncogenes driving tumorigenesis.
  • PTEN (Phosphatase and Tensin homolog) is a critical tumor suppressor regulating the phosphoinositide 3-OH kinase pathway.
  • Ras-mediated tumorigenesis is context-dependent and involves cooperative events.

Purpose of the Study:

  • To investigate the suppressive effect of oncogenic Ras on PTEN expression.
  • To elucidate the signaling pathway mediating Ras-induced PTEN suppression.
  • To determine the role of PTEN's protein phosphatase activity in regulating FAK phosphorylation at Y861.

Main Methods:

  • Established NIH/3T3 cells stably expressing H-Ras mutant proteins.
  • Generated inducible cell lines expressing wild-type PTEN, lipid phosphatase-deficient PTEN, and activity-inert PTEN.
  • Analyzed PTEN protein and transcript levels.
  • Examined Focal Adhesion Kinase (FAK) phosphorylation at Y861 (pY861).

Main Results:

  • Oncogenic H-Ras, K-Ras, and N-Ras suppress PTEN expression at both protein and transcript levels.
  • Ras-mediated PTEN suppression is dependent on the Raf-1/Erk/MEK signaling pathway.
  • PTEN's protein phosphatase activity significantly decreases FAK pY861 levels in H-Ras transformed cells.

Conclusions:

  • Oncogenic Ras actively suppresses the tumor suppressor PTEN via the Raf-1/Erk/MEK pathway.
  • PTEN's phosphatase activity is crucial for regulating FAK phosphorylation at Y861, impacting cell signaling in Ras-driven cancers.

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