PGRMC1 promotes triple-negative breast cancer cell growth via suppressing ferroptosis

Objective Triple-negative breast cancer (TNBC) is the most malignant form of breast cancer with increasing incidence and mortality worldwide. The progesterone receptor membrane component-1 (PGRMC1) is a well-identified hormone receptor with unknown functions in TNBC. The current study aims to explore the involvement of PGRMC1 in regulation of glutathione metabolism and ferroptosis during development of TNBC, providing new therapy options for TNBC patients.Methods Bioinformatic analysis, cell proliferation assay, western blot assay and other biochemistry methods were performed in TNBC cells.Results Our results revealed that the expression of PGRMC1 is higher in TNBC than the other subtypes of breast cancer. Interestingly, as an iron binding protein, increased PGRMC1 expression in TNBC cells leads to resistance to ferroptosis inducer. On the contrary, silenced PGRMC1 expression enhanced sensitivity of MDA-MB231 cells to Erastin. Mechanistically, overexpression of PGRMC1 decreased the intracellular free iron concentration, which was reduced by AG205 treatment.Conclusions PGRMC1 increases the possibility of TNBC development through binding to intracellular iron and suppressing ferroptosis, providing the molecular basis of combined treatment for TNBC.