Inhibition of c-Yes Induces Differentiation of HT-29 Human Colon Cancer Stem Cells through Midbody Elongation

Abstract

Recent research suggests that a small group of cells, named cancer stem cells (CSCs), is responsible for initiating tumor formation, recurrence, and metastasis. c-Yes, a proto-oncogene that is a subfamily of Src family kinase, is often activated in human colon cancer; this implicates c-Yes in the onset and progression of the disease. The objective of this study was to investigate the correlation between c-Yes and CSCs. We performed a sphere formation assay and reverse transcription-polymerase chain reaction for studying the differentiation of HT-29 human colon CSCs. To demonstrate the specific role of c-Yes in CSCs, we performed live cell microscopy and a cell cycle assay. These study shows, for the first time, that c-Yes is enriched in CD133(+) CSCs, compared to their CD133(-) counterparts, and that c-Yes depletion in CD133(+) cells induces cell differentiation. Moreover, c-Yes depletion was found to elongate the midbody and increase the proliferation doubling time. This also suggested that the misregulation of microtubules during chromosomal separation causes aneuploidy. Our results suggest that c-Yes may play a crucial role in initiating, maintaining, and driving the tumorigenic property of colon cancer.