Increased Bcl-xL expression mediates v-Src-induced resistance to anoikis in intestinal epithelial cells

Acquisition of resistance to anoikis (detachment-induced apoptosis) is considered to be a requirement for transformed intestinal epithelial cells to invade surrounding tissues and metastasize to distant organs. Increased Src kinase activity, which is a feature of a large proportion of colorectal cancers, has been identified as one of the factors that can contribute to anoikis resistance. However, the molecular mechanism by which high levels of Src activity contribute to anoikis resistance in intestinal epithelial cells is unknown. Here we show that high Src activity confers resistance to anoikis in intestinal epithelial cells, at least in part, by inducing Bcl-xL overexpression, and that this induction is mediated by the MEK/MAPK pathway. Based on the findings reported here, and on our previous study showing that Bcl-xL plays a critical role in ras-induced resistance to anoikis, we propose that the increased Bcl-xL levels found in colorectal cancers play a significant role in the induction of resistance to anoikis during the progression of this disease.