Prominin 2 promotes the progression of breast cancer by inhibiting ferroptosis via MAPK signaling
Mingchuan Zhao, Juan Jin, Zhonghua Tao, Yannan Zhao, Biyun Wang, Xichun Hu, Hongxia WangAbstract
Background and Objectives
Ferroptosis is an iron-dependent form of programmed cell death, and its dysregulation has been implicated in the progression of breast cancer (BC). Prominin 2 (PROM2) has been reported as a negative regulator of ferroptosis. This study aims to investigate the role of PROM2 in BC progression and its underlying molecular mechanism.
Methods
Bioinformatics analysis was performed to evaluate the expression and prognostic relevance of PROM2 in BC cohort from public database. The expression levels of PROM2 were assessed in BC tissues and cell lines. Knockdown of PROM2 was achieved using lentiviral-mediated shRNA, and the effect of PROM2 silencing in the tumor growth was evaluated in a xenograft model of nude mice.
Results
The results demonstrated that PROM2 was overexpressed in BC tissues and its heightened expression was associated with poor prognosis. Knockdown of PROM2 in BC cell lines suppressed cell proliferation, migration, and invasion, while promoting ferroptosis, as evidenced by increased levels of reactive oxygen species (ROS), lipid peroxidation, and malondialdehyde, as well as decreased levels of glutathione and GPX4 expression. Furthermore, PROM2 was found to activate the mitogen-activated protein kinase (MAPK) signaling pathway, and inhibition of this pathway abrogated the pro-tumorigenic effects of PROM2 overexpression.
Conclusions
Collectively, our findings pinpoint a crucial role of PROM2 in BC progression by inhibiting ferroptosis and activating the MAPK signaling pathway. Targeting PROM2 might represent a potential therapeutic strategy for BC treatment.