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Despite advancements, the precise mechanisms driving PM carcinogenesis remain elusive, impeding therapeutic progress. Here, we explore the interplay between tumor growth dynamics, lipid metabolism, and NF-\u03baB dysregulation in malignant pleural mesothelioma, shedding light on novel molecular mechanisms underlying its pathogenesis. Our study reveals distinctive growth dynamics in PM cells, characterized by heightened proliferation, altered cell cycle progression, and resistance to apoptosis. Intriguingly, PM cells exhibit increased intracellular accumulation of myristic, palmitic, and stearic acids, suggestive of augmented lipid uptake and altered biosynthesis. Notably, we identify FABP5 as a key player in driving metabolic alterations and inflammation through NF-\u03baB dysregulation in mesothelioma cells, distinguishing them from normal mesothelial cells. Silencing of FABP5 leads to significant alterations in cell dynamics, metabolism, and NF-\u03baB activity, highlighting its potential as a therapeutic target. Our findings unveil a reciprocal relationship between lipid metabolism and inflammation in PM, providing a foundation for targeted therapeutic strategies. Overall, this comprehensive investigation offers insights into the intricate molecular mechanisms driving PM pathogenesis and identifies potential avenues for therapeutic intervention.<\/jats:p>","DOI":"10.1038\/s42003-025-07754-0","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T07:52:57Z","timestamp":1740729177000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["FABP5 is a key player in metabolic modulation and NF-\u03baB dependent inflammation driving pleural mesothelioma"],"prefix":"10.1038","volume":"8","author":[{"given":"Eleonora","family":"Vecchio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selena","family":"Mimmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3541-1830","authenticated-orcid":false,"given":"Debora","family":"Gentile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8681-8230","authenticated-orcid":false,"given":"Caterina","family":"Giordano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4583-863X","authenticated-orcid":false,"given":"Emilio","family":"Straface","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Marino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Caiazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Pastore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosaria","family":"Ruocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Arcucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Schiavone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6707-4723","authenticated-orcid":false,"given":"Camillo","family":"Palmieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Iaccino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano","family":"Stornaiuolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana","family":"Quinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4001-3856","authenticated-orcid":false,"given":"Massimo","family":"Mallardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Martini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Tognon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5414-6190","authenticated-orcid":false,"given":"Giuseppe","family":"Fiume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"7754_CR1","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1158\/2159-8290.CD-11-0102","volume":"1","author":"D Guo","year":"2011","unstructured":"Guo, D. et al. 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