FABP5 is a key player in metabolic modulation and NF-κB dependent inflammation driving pleural mesothelioma

被引:0
作者
Vecchio, Eleonora [1 ]
Gallo, Raffaella [1 ]
Mimmi, Selena [1 ]
Gentile, Debora [1 ]
Giordano, Caterina [1 ]
Straface, Emilio [1 ]
Marino, Rossana [2 ]
Caiazza, Carmen [2 ]
Pastore, Arianna [3 ]
Ruocco, Maria Rosaria [2 ]
Arcucci, Alessandro [4 ]
Schiavone, Marco [5 ]
Palmieri, Camillo [1 ]
Iaccino, Enrico [1 ]
Stornaiuolo, Mariano [3 ]
Quinto, Ileana [1 ]
Mallardo, Massimo [2 ]
Martini, Fernanda [6 ]
Tognon, Mauro [6 ]
Fiume, Giuseppe [1 ]
机构
[1] Univ Catanzaro Magna Graecia, Dept Expt & Clin Med, Catanzaro, Italy
[2] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy
[3] Univ Naples Federico II, Dept Pharm, Naples, Italy
[4] Univ Naples Federico II, Dept Publ Hlth, Naples, Italy
[5] Univ Brescia, Dept Mol & Translat Med, Zebrafish Facil, Brescia, Italy
[6] Univ Ferrara, Dept Med Sci, Ferrara, Italy
关键词
ACID-BINDING PROTEIN; PROMOTES CELL-PROLIFERATION; THERAPEUTIC TARGET; LIPID-METABOLISM; CANCER-CELLS; ACTIVATION; EXPRESSION; MUTATIONS; SYNTHASE; SURVIVAL;
D O I
10.1038/s42003-025-07754-0
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pleural mesothelioma (PM) 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 PM carcinogenesis remain elusive, impeding therapeutic progress. Here, we explore the interplay between tumor growth dynamics, lipid metabolism, and NF-kappa B 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-kappa B dysregulation in mesothelioma cells, distinguishing them from normal mesothelial cells. Silencing of FABP5 leads to significant alterations in cell dynamics, metabolism, and NF-kappa B 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.
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页数:13
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