FABP5 is a Novel Key Player in Metabolic Modulation and NF-κB dependent Inflammation driving Malignant Pleural Mesothelioma

Abstract Malignant pleural mesothelioma (MPM) poses a significant challenge in oncology due to its intricate molecular and metabolic landscape, chronic inflammation, and heightened oxidative stress, which contribute to its notorious resilience and clinical complexities. Despite advancements, the precise mechanisms driving MPM carcinogenesis remain elusive, impeding therapeutic progress. Here, we explore the interplay between tumor growth dynamics, lipid metabolism, and NF-κB dysregulation in malignant pleural mesothelioma, shedding light on novel molecular mechanisms underlying its pathogenesis. Our study reveals distinctive growth dynamics in MPM cells, characterized by heightened proliferation, altered cell cycle progression, and resistance to apoptosis. Intriguingly, MPM cells exhibit increased intracellular accumulation of myristic, palmitic, and stearic acids, suggestive of augmented lipid uptake and altered biosynthesis. Notably, we identify FABP5 as key player in driving metabolic alterations and inflammation through NF-κB dysregulation in mesothelioma cells, distinguishing them from normal mesothelial cells. Silencing of FABP5 leads to significant alterations in cell dynamics, metabolism, and NF-κB activity, highlighting its potential as therapeutic target. Our findings unveil a reciprocal relationship between lipid metabolism and inflammation in MPM, providing a foundation for therapeutic strategies. Overall, this comprehensive investigation offers insights into the intricate molecular mechanisms driving MPM pathogenesis and identifies potential avenues for therapeutic intervention.