Language

English

Publication Date

8-10-2026

Journal

Cancer Letters

DOI

10.1016/j.canlet.2026.218562

PMID

42092682

PMCID

PMC13241086

PubMedCentral® Posted Date

6-6-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Cigarette smoke promotes bladder tumor growth by enhancing cancer cell survival and proliferation through smoke mediated carcinogens. FASN, a key enzyme in fatty acid synthesis, is dysregulated in many cancers and correlates with aggressive phenotypes. In this study, we demonstrate elevated fatty acid levels and FASN specifically in smokers with bladder cancer. Elevated FASN under smoke exposure imparted epigenetic alterations, particularly histone acetylation, impacts DNA repair and DNA-binding transcription factors which regulate metabolic pathways. Under cigarette smoke, bladder cancer cells undergo a metabolic shift, utilizing glutamine as a major carbon source through reductive carboxylation to fuel fatty acid biosynthesis via FASN. Genetic and pharmacological inhibition of FASN significantly reduced tumor growth in a chicken embryo Chorio-allantoic Membrane model exposed to smoke. FASN inhibitors such as TVB-2640, currently in clinical trials, may represent an effective therapeutic strategy for smokers with bladder cancer exhibiting high FASN levels.

Keywords

Humans, Urinary Bladder Neoplasms, Animals, Fatty Acids, Metabolic Reprogramming, Fatty Acid Synthase, Type I, Disease Progression, Cell Line, Tumor, Chick Embryo, Smoke, Cell Proliferation, Epigenesis, Genetic, Cigarette Smoking, DNA Repair, Histones, Cigarette smoke, FASN, Fatty acid metabolism, Bladder cancer, DNA damage and repair

Published Open-Access

yes

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