c-Myc maintains the self-renewal and chemoresistance properties of colon cancer stem cells

Cancer stem cells (CSCs) are responsible for cancer formation, recurrence and drug resistance. c-Myc, one of the core markers for stem cells, has recently been considered to serve as a link between malignancy and ‘stemness’. However, the precise function of c-Myc in colon CSCs is still unclear. In the present study, a subpopulation of colon CSCs expressing a CD133 surface phenotype was isolated from the human HT-29 cell line, which possess greater tumor sphere-forming efficiency and have higher expression of ‘stemness’-associated genes compared with CD133-negative cells. Furthermore, it was demonstrated that c-Myc was highly expressed in CD133(+) colon CSCs. Knockdown of c-Myc expression with small interfering RNA in colon CSCs can significantly inhibit tumor sphere formation, reduce the invasive and migratory capacity of CD133(+) cells in vitro, and suppress the tumorigenicity of colon CSCs in vivo. In addition, it was suggested that c-Myc silencing may sensitize colon CSCs to chemotherapy-induced cytotoxicity via the downregulation of ABCG2 and ABCB5. These findings support a central role for c-Myc in maintaining the self-renewing and chemoresistant properties of colon CSCs.