Transforming growth factor-beta increases breast cancer stem cell population partially through upregulating PMEPA1 expression

The prostate transmembrane protein, androgen-induced 1 (PMEPA1) has been previously shown to promote solid malignancies in a variety of cancers, but the role and mechanisms of PMEPA1 in breast cancer has not been fully addressed. Here, we found that PMEPA1 was upregulated in breast cancer cell lines as well as in a set of clinical invasive breast ductal carcinomas. Interestingly, depletion of PMEPA1 decreased breast cancer stem cell (CSC)-enriched populations, while ectopic overexpression of PMEPA1 increased breast CSC-enriched populations. Furthermore, transforming growth factor-β (TGF-β) treatment was also found to upregulate PMEPA1 expression and the CSC-enriched populations in triple-negative breast cancer cell lines. TGF-β-induced PMEPA1 expression partially contributed to TGF-β-induced breast CSC maintenance. These findings suggest that TGF-β-PMEPA1 axis might provide new diagnosis and therapeutic targets for breast cancer treatment.