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Overexpression of Csk-binding protein contributes to renal cell carcinogenesis

Oncogene volume 28, pages 3320–3331 (2009)Cite this article

Abstract

C-terminal Src kinase (Csk)-binding protein (Cbp) is a transmembrane adaptor protein that localizes exclusively in lipid rafts, where it regulates Src family kinase (SFK) activities through recruitment of Csk. Although SFKs are well known for their involvement in cancer, the function of Cbp in carcinogenesis remains largely unknown. In this study, we reported overexpression of Cbp in more than 70% of renal cell carcinoma (RCC) specimens and in the majority of tested RCC cell lines. Depletion of Cbp in RCC cells by RNA interference led to remarkable inhibition of cell proliferation, migration, anchorage-independent growth as well as tumorigenicity in nude mice. Strikingly, silencing of Cbp negatively affected the sustaining of Erk1/2 activation but not c-Src activation induced by serum. Besides, the RhoA activity in RCC cells was remarkably impaired when Cbp was knocked down. Overexpression of wild-type Cbp, but not its mutant Cbp/ΔCP lacking C-terminal PDZ-binding motif, significantly enhanced RhoA activation and cell migration of RCC cells. These results provided new insights into the function of Cbp in modulating RhoA activation, by which Cbp might contribute to renal cell carcinogenesis.

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Acknowledgements

We thank Dr Vaclav Horejsi (Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic) for kindly and generously giving us the monoclonal antibody against Cbp. This work was supported by grants from National Natural Science Foundation of China (30730055 and 30623002), National Key Scientific Program of China (2007CB914504), the Chinese Academy of Sciences (KSCX1-YW-R-67, KSCX2-YW-R-108), Program of Shanghai Subject Chief Scientist (08XD14051) and the National High Technology Research and Development Programme of China (2006AA02A308).

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Author notes

  1. L Q Jiang

    Present address: 6Current address: The Department of physiology and pharmacology, Section of Integrative Physiology, Karolinska Institute, Stockholm, Sweden.,

  2. X Feng and X Lu: These authors contributed equally to this work.

Authors and Affiliations

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

    X Feng, X Lu, W Zhou, L Q Jiang, L Lei, Q Huang, Z Zhang & Z Chen

  2. Graduate University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China

    X Feng, X Lu, W Zhou, L Lei & Q Huang

  3. International Co-operation Laboratory on Signal Transduction, Eastern Hepotabiliary Surgical Institute, The Second Military Medical University, Shanghai, China

    X Man

  4. Department of Molecular Biology, Max-Planck-Institute of Biochemistry, Martinsried, Germany

    P Knyazev & A Ullrich

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Correspondence to Z Zhang or Z Chen.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Feng, X., Lu, X., Man, X. et al. Overexpression of Csk-binding protein contributes to renal cell carcinogenesis. Oncogene 28, 3320–3331 (2009). https://doi.org/10.1038/onc.2009.185

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