Elevated c-Src is linked to altered cell-matrix adhesion rather than proliferation in KM12C human colorectal cancer cells.
Elevated expression and/or activity of c-Src, the prototype of the Src family of protein tyrosine kinases, is associated with the development of human colon cancer. However, despite the known pleiotropic effects of these kinases in promoting (a) cell growth downstream of growth factor receptors, and (b) the dynamic regulation of integrin adhesions in fibroblast model systems, their precise role in epithelial cancer cells is unknown. Here we addressed whether elevated expression and activity of cellular Src alters cell proliferation and/or cell-matrix adhesion in cancer cells from the Fidler model of colorectal metastasis. Although elevated Src correlates with ability to metastasise to the liver after intrasplenic injection, we found that this was not linked to enhanced growth, either in vitro or in vivo as sub-cutaneous tumours. However, elevated Src was associated with enhanced attachment to extracellular matrix. In addition, adhesion to fibronectin, was suppressed by agents that inhibited Src activity, while enforced elevation of Src in non-metastatic cells was sufficient to stimulate adhesion to fibronectin and enhanced assembly of adhesion complexes, without influencing cell growth. Thus, we conclude that one role of elevated Src in human colon cancer cells is to modulate integrin-dependent cell-matrix attachment and formation of adhesion structures, which may, in turn, influence cell motility and integrin-dependent cellular responses.
Jones
R J
RJ
Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, Scotland, UK.
Avizienyte
E
E
Wyke
A W
AW
Owens
D W
DW
Brunton
V G
VG
Frame
M C
MC
D002448:Cell Adhesion; D021982:Cell-Matrix Junctions / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009362:Neoplasm Metastasis; D015688:Oncogene Protein pp60(v-src) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D014407:Tumor Cells, Cultured
D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)