Regulation of 15-PGDH by ACSM1 in modulating PGE2 signaling and ECM remodeling in prostate cancer

Prostate cancer remains one of the most common and aggressive cancers worldwide, but the molecular mechanisms underlying its progression are not yet fully understood. The ACSM1 gene is intimately associated with the development of prostate cancer. Here we demonstrated that down-regulation of ACSM1 expression in LNCaP prostate cancer cells significantly inhibits cell proliferation and migration, while overexpression enhances these processes in normal cells. Interestingly, the subcellular localization shift of ACSM1 to cytoplasm coincides with its interaction with 15-PGDH. Overexpression of ACSM1 also decreases 15-PGDH levels, increasing PGE2 production and altering ECM-related factors. Overexpression of 15-PGDH reverses these effects, suppressing the proliferation and migration of LNCaP cells. With specific PGE2 receptor inhibitors, AH6809 significantly affects the proliferation and migration of LNCaP cells with high ACSM1 expression. Based on our results, it appears that ACSM1 regulates prostate cancer cell behavior via the 15-PGDH-mediated PGE2 signaling pathway and Extracellular Matrix (ECM) remodeling.