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Updated: Jul 5, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

The lipid raft-anchored adaptor protein Cbp controls the oncogenic potential of c-Src

Chitose Oneyama1, Tomoya Hikita, Kengo Enya

  • 1Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.

Molecular Cell
|May 24, 2008
PubMed

Insights

Cbp acts as a tumor suppressor by binding to and sequestering the oncogenic tyrosine kinase c-Src in lipid rafts, independent of Csk. Restoring Cbp levels inhibits c-Src-driven cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The tyrosine kinase c-Src is frequently upregulated in human cancers, contributing to oncogenicity.
  • The precise regulatory mechanisms controlling c-Src's oncogenic potential, particularly its interaction with regulators like Csk, remain incompletely understood.

Purpose of the Study:

  • To investigate the role of the Csk adaptor Cbp/PAG in regulating the oncogenic activity of c-Src.
  • To elucidate the mechanism by which Cbp influences c-Src-mediated transformation and tumorigenesis.

Main Methods:

  • Utilized Csk-deficient cells for studying c-Src transformation.
  • Assessed the impact of Cbp expression levels on c-Src transformation and tumorigenesis.
  • Investigated the interaction between phosphorylated Cbp and activated c-Src in lipid rafts.
  • Examined Cbp expression in human cancer cells and tumors.

Main Results:

  • c-Src activation downregulates Cbp expression; Cbp re-expression suppresses c-Src transformation and tumorigenesis.
  • Cbp-deficient cells exhibit increased susceptibility to v-Src transformation.
  • Phosphorylated Cbp binds activated c-Src, sequestering it within lipid rafts, thereby inhibiting c-Src function independently of Csk.
  • Cbp is downregulated in some human cancers, and its introduction suppresses tumor growth.

Conclusions:

  • Cbp functions as a critical suppressor of c-Src oncogenic activity.
  • Cbp sequesters activated c-Src in lipid rafts, providing a Csk-independent regulatory mechanism.
  • Cbp represents a potential therapeutic target for inhibiting c-Src-mediated tumor progression.

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