Autophagy maintains the stemness of ovarian cancer stem cells by FOXA2.

Abstract

Abstract Background Cancer stem cells (CSCs) are regarded as the main cell type responsible for the initiation, metastasis, drug resistance, and recurrence of cancer. But the mechanism by which cancer stem cells maintain their stemness remains unclear. Methods and Results In the present study, ovarian cancer stem cells (OCSCs) were revealed to have an enhanced autophagic flux. Furthermore, their chemoresistance and ability to self-renewal in vitro were decreased when autophagy was inhibited by Bafilomycin A1(BafA1), Chloroquine(CQ) or autophagy related 5(ATG5) knockdown. PCR array screening determined that Forkhead Box A2(FOXA2) was highly expressed in OCSCs, and correspondingly regulated by autophagy activity. In addition, the self-renewal ability was decreased in the case of FOXA2 knockdown by shRNA in OCSCs. Overexpression of FOXA2 from the pEGFP(+)-FOXA2 plasmid partially reversed the depressed self-renewal ability of OCSCs during autophagy inhibition. Conclusions Our findings suggest that autophagy, through participation of FOXA2, maintains the characteristics of OCSCs. Autophagy and FOXA2 are therefore potential targets for ovarian cancer stem cell directed therapies.

Keywords

• Autophagy
• Ovarian cancer
• Cancer stem cell
• FOXA2
• Stemness