1. ¹Department of Biochemistry and Molecular Biology, and Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada
2. ²Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia

Correspondence: Dr DJ Fujita, Department of Biochemistry and Molecular Biology, University of Calgary Health Sciences Centre, 3330 Hospital Dr, NW, Calgary, Alberta, Canada T2N 4N1. E-mail: dfujita@ucalgary.ca

Received 23 October 2006; Revised 30 August 2007; Accepted 3 September 2007; Published online 15 October 2007.

Abstract

Src activation has been associated with colon cancers but the mechanism underlying Src activation is largely unknown. Csk-homologous kinase (CHK) can inhibit the kinase activity of certain Src kinase family members in vitro by phosphorylating the C-terminal tyrosine and by a non-catalytic mechanism. CHK was previously reported to be expressed primarily in brain and hematopoietic cells. We report herein that CHK is also expressed in normal colon cell lines. Furthermore, CHK protein levels are significantly decreased in various colon cancer cell lines and the decrease correlates with the increased specific activity of Src in these cell lines, while the level of the other Src inhibitory kinase, C-terminal Src kinase, is not significantly changed. CHK is also expressed in normal colon tissues but its expression level is decreased in colon cancer tissues collected from the same patients. Immunofluorescence microscopy shows that CHK colocalizes with Src in normal colon FHC cells. Overexpression of CHK in colon cancer cells results in inactivation of Src without phosphorylating Y530 at its C-terminus. In addition, CHK suppresses anchorage-independent cell growth and cell invasion of colon cancer cells. These results reveal a potentially important role for CHK in Src activation and tumorigenicity in colon cancer cells.