Estrogen regulates PDPK1 to promote cell proliferation in epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is a common estrogen-sensitive tumor that poses a serious threat to women 's health, and the mortality rate of EOC ranks first among malignant tumors in females. Studies have indicated a strong link between estrogen abnormality and EOC progression. We accidently found that 3-phosphoinositide-dependent protein kinase-1 (PDPK1) is highly expressed in EOC tissues. Further, estrogen also up-regulates the expression of PDPK1 in EOC cells. Notably, the expression of PDPK1 is controlled strictly, and its expression can determine the fate of cells. However, to date, the molecular mechanism by which estrogen elicits PDPK1 expression in EOC cells, and the role of PDPK1 in estrogen-driven EOC cells are not well defined. In this research, we found that a high expression of PDPK1 was associated with poor prognosis in patients with ovarian cancer. Further, estrogen stimulated the increase of PDPK1 protein expression through estrogen receptor ESR1. The depletion or overexpression of PDPK1 affected the inhibition or amplification of estrogen-driven EOC cell proliferation, and the knockdown of PDPK1 suppressed the migration of EOC cells by estrogen while promoting cell apoptosis. This suggests a critical functional association between estrogen and PDPK1 in the process of EOC. The expression of messenger RNA for cyclin A1, cyclin-dependent kinase 2 (CDK2), matrix metallopeptidase 2 (MMP2), and bcl-2 associated x protein (Bax) is regulated by PDPK1 under estrogen treatment. Our results indicated that PDPK1 plays a role as an oncogene in the development of EOC; hence, elucidating the mechanism by which estrogen promotes EOC progression by regulating PDPK1 expression.