Decreased CHK protein levels are associated with Src activation in colon cancer cells

• Published in: Oncogene Vol. 27; no. 14; pp. 2027 - 2034
• Main Authors: Zhu, S, Bjorge, J D, Cheng, H C, Fujita, D J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.03.2008; Nature Publishing; Nature Publishing Group
• Subjects: Apoptosis; Biological and medical sciences; C-Terminus; Cancer cells; Cell activation; Cell Biology; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular biology; Colon cancer; Colonic Neoplasms - enzymology; Colonic Neoplasms - pathology; Colorectal cancer; Down-Regulation; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; Genetic aspects; Genetics; Human Genetics; Humans; Immunofluorescence; Internal Medicine; Kinases; Medical sciences; Medicine; Medicine & Public Health; Molecular and cellular biology; Neoplasm Invasiveness; Oncology; original-article; Phosphorylation; Physiological aspects; Protein kinases; Proteins; Proto-Oncogene Proteins pp60(c-src) - analysis; Proto-Oncogene Proteins pp60(c-src) - metabolism; Src protein; src-Family Kinases - analysis; src-Family Kinases - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor cell lines; Tumorigenicity; Tumors; Tyrosine; Canada; src; colon cancer; CHK; Enzyme; Transferases; Activation; Malignant tumor; Carcinogenesis; Protein; Colonic disease; Colon cancer; Digestive diseases; Intestinal disease; Protein-tyrosine kinase; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210838

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.