Estrogen receptor alpha (ERα) is a hormone receptor that functions as a ligand-activated transcription factor to regulate the expression of a wide variety of estrogen-responsive genes in target cells. Dysregulated ERα expression or activity is closely linked to the malignant transformation of hormone-regulated cells. However, it is unknown whether the changes in ERα expression or activity impact the function of metabolic enzymes in cancer cells. In this study, we focus on the role of ERα modulating PKM2 and FASN expression in cancer cells and the impacts of their expression on cell proliferation. Our data clearly showed that knockdown of ERα led to decreases in the expression of PKM2 and FASN in breast cancer MCF-7 cells, prostate cancer PC-3 cells, and oral cancer OECM-1 cells. Moreover, the decrease in PKM2 or FASN expression was correlated with reduced cell proliferation in ERα-knockdown cells. Treatment of 17β-estradiol (E2) upregulated the expression of PKM2 and FASN in cancer cells and promoted their proliferation, while the E2-promoted effects on PKM2 or FASN expression as well as cell proliferation could be abolished by treatment with tamoxifen. Interestingly, knockdown of FASN or PKM2 expression in cancer cells caused decreased ERα expression and impacted each other’s expression and cell proliferation. In summary, our data suggested that the reciprocal regulation of expression among ERα, PKM2, and FASN impacted the proliferation of cancer cells.

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