Insider Influence on ErbB Activity

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell (Impact Factor: 32.24). 10/2010; 143(2):181-2. DOI: 10.1016/j.cell.2010.09.042
Source: PubMed


The receptor tyrosine kinase ErbB is activated by ligand-induced dimerization, leading to transphosphorylation of the cytoplasmic kinase domains. Bill et al. (2010) now demonstrate that transphosphorylation can be modulated from within the cell by the cytoplasmic protein cytohesin, providing new insights into ErbB-dependent processes during normal development and cancer.

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    ABSTRACT: Objective: To investigate the effect of cytohesins on proliferation of colorectal cancer cells, and to explore its possible mechanism. Methods: The expressions of cytohesins in colorectal cancer HT-29, SW620, SW480 and HCT-116 cells were detected by RT-PCR and immunofluorescence. The proliferative activity of colorectal cancer HT-29 cells was detected by MTT method after SecinH3 or cytohesin-siRNA intervention. The activation of epidermal growth factor receptor (EGFR) signal pathway in HT-29 cells and the activation of insulin-like growth factor type I receptor (IGF-IR) signal pathway in HCT-116 cells were detected by Western blotting. Results: The colorectal cancer HT-29, SW620, SW480 and HCT-116 cells expressed four homologous members of cytohesins, in which the cytohesin-2 (ARNO) exerted a highest level. The proliferative-inhibiton rates of HT-29 cells blocked by SecinH3 for 72 h and interfered with ARNO-siRNA for 48 h were (57.22±1.01)% and (58.95±3.42)%, respectively; furthermore, the expression of ARNO protein was significantly decreased, and the EGFR and IGF-IR signaling pathways were both inhibited with down-regulation of factors in the corresponding downstream pathways. Conclusion: Cytohesins are associated with the activation of EGFR and IGF-IR signaling pathways, and the cytohesins maybe serve as a new molecular target in the treatment of colorectal cancer.
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