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

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.

Denbinobin suppresses breast cancer metastasis through the inhibition of Src-mediated signaling pathways

“…Under normal physiological condition, 90-95% of Src is in an inactive conformation [5]. However, activated Src is frequently reported in human cancers, including colon adenocarcinoma [6], breast cancer [7] and pancreatic cancer [8]. In the case of breast cancer, increased Src activity is believed to play an important role in development and progression [4,5].…”

Src family tyrosine kinases-driven colon cancer cell invasion is induced by Csk membrane delocalization

“…Nevertheless, the involvement of Csk in CRC remains controversial. Indeed, Csk level was found either downregulated or upregulated in CRC tumours (Be´nistant et al, 2001;Cam et al, 2001;Zhu et al, 2008), inconsistent with a potential tumour suppressor function. This notion is reinforced by the detection of Csk autoantibodies in some patients with CRC, indicating that this tyrosine kinase is a novel tumour antigen in this cancer (Be´nistant et al, 2001).…”

Acetylcholine-induced activation of M3 muscarinic receptors stimulates robust matrix metalloproteinase gene expression in human colon cancer cells

“…It requires fewer extracellular growth factors and is independent of cell-cell interaction (30). Hence, measurement of anchorage-independent growth is considered an accurate and stringent test for uncontrolled cell proliferation (18,20,39). To determine whether ACh promotes anchorage-independent growth of H508 colon cancer cells, we used a soft agar assay (see MATERIALS AND METHODS).…”