The Role of EMP2 in Triple-negative Breast Cancer

The poor prognosis of triple-negative breast cancer (TNBC) is largely due to the lack of targeted therapies, as a result of the absence of estrogen, progesterone, and HER2 receptors. Our previous studies highlighted Del-1 as a potential therapeutic target and biomarker for TNBC. This study further explores molecules regulated by Del-1 through transcriptomic analysis. After silencing Del-1 expression using siRNA across multiple TNBC cell lines, RNA was sequenced to identify potential candidate gene groups. EMP2 was the most up-regulated in Del-1 knockdown TNBC cell lines and selected as the final candidate gene. Subsequent knockdown experiments targeting Del-1 and EMP2 were conducted to elucidate their roles in cellular functions. Furthermore, the expression of cancer stem cell markers, ALDH and Nanog, was evaluated after Del-1 knockdown. Del-1 and EMP2 expression was increased in TNBC cell lines compared to normal breast cell MCF10A. RNA sequencing revealed an inverse relationship between the two genes, which was substantiated by separate knockdown experiments. EMP2 knockdown using siRNA in MB468 and MB231 cells decreased proliferation in both groups. Colony formation assays, conducted to evaluate the survival and proliferative capacity of individual cells, demonstrated improved colony formation in the EMP2-knockdown group. The expression of cancer stem cell markers ALDH and Nanog in MB231 cells increased after Del-1 knockdown. Del-1 and EMP2 are over-expressed in TNBC and show an inverse regulatory relationship. Del-1 knockdown promotes stemness features, while EMP2 knockdown reduces proliferation and increases chemosensitivity. These findings highlight the Del-1/EMP2 axis as a potential regulatory pathway in TNBC progression and resistance, suggesting that EMP2 may serve as a novel therapeutic target.