The PPARβ/CERK/C1P signaling pathway is a potential mechanism by which antimony exposure promotes prostate cancer...

Prostate cancer (PCa) is the most common malignant tumor in males. Antimony (Sb) is a widespread industrial heavy metal pollutant listed as a Class IIB carcinogen by the International Agency for Research on Cancer (IARC). Previous work found that antimony exposure can promote the proliferation of prostate cancer cells, but the relevant molecular mechanisms have not been fully explored. Lipid metabolomic sequencing revealed that ceramide levels were significantly elevated in PCa cells after low-dose antimony exposure. To explore the relationship between antimony exposure and cell proliferation, we found that the level of ceramide-1-phosphate (C1P), one of the metabolites of ceramide, increased after antimony exposure, and C1P can promote the proliferation of prostate cancer cells and antagonize the apoptosis induced by ceramide. Mechanism exploration shows that antimony exposure activates peroxisome proliferator-activated receptor beta (PPARβ), up-regulates the expression levels of ceramide transport protein (CERT) and ceramide kinase (CERK), promotes the conversion of Cer to C1P, thereby inhibiting apoptosis and promoting PCa cells proliferation. In addition, we also found that C1P can partially inhibit ferroptosis induced by erastin. These findings indicate that C1P is closely related to antimony-induced PCa proliferation and may be a potential biomarker of PCa.