alpha-Actinin-4 regulates cancer stem cell properties and chemoresistance in cervical cancer

Abstract

Cancer stem cells (CSCs) initiate tumors and possess the properties of self-renewal and differentiation. Since they are responsible for chemoresistance, CSCs are known to be a key factor in cancer recurrence. alpha-Actinin-4 (ACTN4) is an actin-binding protein that is involved in muscle differentiation and cancer metastasis. It promotes epithelial to mesenchymal transition and cell cycle progression via beta-catenin stabilization in cervical cancer. In the present study, we investigated the role of ACTN4 in regulating cancer cell stemness and chemoresistance in cervical cancer. Results from the gene expression database analysis showed that ACTN4 mRNA expression was elevated in cancerous cervices when compared with normal cervices. Furthermore, ACTN4 knockdown suppressed sphere formation and CSC proliferation. It also decreased CSC size and CD44(high)/CD24(low) cell population. ACTN4-knockdown CSCs were sensitive to anticancer drugs, which was observed by down-regulation of the ATP-binding cassette family G2 involved in drug resistance. Finally, ACTN4-knockdown CSCs formed reduced tumors in vivo when compared with control CSCs. Overall, these findings suggest that ACTN4 regulates CSC properties and contributes to chemoresistance in cervical cancer.