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

Med Oncol. 2025 Jun 28;42(8):297. doi: 10.1007/s12032-025-02866-3.

Abstract

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.

Keywords: 15-PGDH; ACSM1; ECM; PGE2; Prostate cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Dinoprostone* / metabolism
  • Extracellular Matrix* / metabolism
  • Extracellular Matrix* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hydroxyprostaglandin Dehydrogenases* / genetics
  • Hydroxyprostaglandin Dehydrogenases* / metabolism
  • Intramolecular Oxidoreductases* / genetics
  • Intramolecular Oxidoreductases* / metabolism
  • Male
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Signal Transduction / physiology

Substances

  • Dinoprostone
  • 15-hydroxyprostaglandin dehydrogenase
  • Hydroxyprostaglandin Dehydrogenases
  • Intramolecular Oxidoreductases