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Overexpression of Csk-binding protein contributes to renal cell carcinogenesis

X Feng1, X Lu, X Man

  • 1State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Oncogene
|July 8, 2009
PubMed

Insights

C-terminal Src kinase (Csk)-binding protein (Cbp) is overexpressed in renal cell carcinoma (RCC). Reducing Cbp inhibits RCC cell growth, migration, and tumor formation by affecting RhoA activation.

Area of Science:

  • Molecular biology
  • Oncology
  • Cell signaling

Background:

  • C-terminal Src kinase (Csk)-binding protein (Cbp) is a transmembrane adaptor protein regulating Src family kinase (SFK) activity.
  • The role of Cbp in cancer, particularly renal cell carcinoma (RCC), is not well understood.

Purpose of the Study:

  • To investigate the role of Cbp in the development and progression of renal cell carcinoma.
  • To elucidate the molecular mechanisms by which Cbp influences RCC cell behavior.

Main Methods:

  • Quantitative analysis of Cbp expression in RCC specimens and cell lines.
  • RNA interference (RNAi) to deplete Cbp in RCC cells.
  • Assessment of cell proliferation, migration, anchorage-independent growth, and tumorigenicity.
  • Analysis of signaling pathways including Erk1/2, c-Src, and RhoA activation.

Main Results:

  • Cbp is overexpressed in over 70% of RCC specimens and most RCC cell lines.
  • Cbp depletion significantly inhibited RCC cell proliferation, migration, anchorage-independent growth, and tumorigenicity.
  • Silencing Cbp impaired sustained Erk1/2 activation and markedly reduced RhoA activity.
  • Overexpression of wild-type Cbp, but not a Cbp mutant lacking the PDZ-binding motif, enhanced RhoA activation and cell migration.

Conclusions:

  • Cbp plays a significant role in renal cell carcinoma progression.
  • Cbp contributes to RCC carcinogenesis, at least in part, by modulating RhoA activation.
  • Cbp represents a potential therapeutic target for renal cell carcinoma.

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