FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma

作者：Chianese U, Papulino C, Ali A, Ciardiello F, Cappabianca S, Altucci L, Carafa V, Benedetti R · 发表于：Journal of translational medicine · 年份：2023 · DOI：10.1186/s12967-023-03874-5 · 研究领域：FASN、Metabolism、Pancreatic adenocarcinoma、Proliferation、Prostate adenocarcinoma

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) and prostate cancer (PCa) are among the most prevalent malignant tumors worldwide. There is now a comprehensive understanding of metabolic reprogramming as a hallmark of cancer. Fatty acid synthase (FASN) is a key regulator of the lipid metabolic network, providing energy to favor tumor proliferation and development. Whereas the biological role of FASN is known, its response and sensitivity to inhibition have not yet been fully established in these two cancer settings. METHODS: To evaluate the association between FASN expression, methylation, prognosis, and mutational profile in PDAC and PCa, we interrogated public databases and surveyed online platforms using TCGA data. The STRING database was used to investigate FASN interactors, and the Gene Set Enrichment Analysis platform Reactome database was used to perform an enrichment analysis using data from RNA sequencing public databases of PDAC and PCa. In vitro models using PDAC and PCa cell lines were used to corroborate the expression of FASN, as shown by Western blot, and the effects of FASN inhibition on cell proliferation/cell cycle progression and mitochondrial respiration were investigated with MTT, colony formation assay, cell cycle analysis and MitoStress Test. RESULTS: The expression of FASN was not modulated in PDAC compared to normal pancreatic tissues, while it was overexpressed in PCa, which also displayed a different level of promoter methylation. Based on tum...