Медицинская библиотека · Cancer letters · 2026

Cigarette smoke induces FASN-dependent fatty acid metabolic rewiring to drive bladder cancer progression.

Amara Chandra Sekhar, Piyarathna Danthasinghe Waduge Badrajee, Kamal Abu Hena Mostafa, Chan Yuen San, Kami Reddy Karthik Reddy, Ambati Chandra Shekar R, Hassan Mohammed Khurshidul, Shriwas Pratik, Gandhi Tanmay, Jain Antrix, Gangnus Tanja, Popli Pooja, Borkar Roshan, Kang Sung Wook, Summers Silvia L, Putluri Vasanta, Grimm Sandra L, Venkatesh Sharan, Song Ningxin, Seeley Erin H, Hedlich-Dwyer Jenna, Chen Shu-Hsia, Mahajan Nupam P, Jain Abhinav K, Dobrolecki Lacey Elizabeth, Wells Gabrielle A, Villanueva Hugo, Li Jenny, Liu Xuefeng, Bollag Roni J, Malovannaya Anna, Jung Sung Yun, Lee Hyun-Sung, Asangani Irfan A, Terris Martha K, Creighton Chad J, Ballester Leomar Y, Karanam Balasubramanyam, Liu Suyu, Lee MinJae, Raju Rajeeva R, Siddiqui M Minhaj, Eberlin Livia S, Kommagani Ramakrishna, Sreekumar Arun, Gao Jianjun, Young Nicolas L, Hodges H Courtney, Coarfa Cristian, Gassman Natalie R, Lerner Seth P, Lotan Yair, Putluri Nagireddy

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Аннотация

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.

Для цитирования: Amara Chandra Sekhar, Piyarathna Danthasinghe Waduge Badrajee, Kamal Abu Hena Mostafa, Chan Yuen San, Kami Reddy Karthik Reddy, Ambati Chandra Shekar R, Hassan Mohammed Khurshidul, Shriwas Pratik, Gandhi Tanmay, Jain Antrix, Gangnus Tanja, Popli Pooja, Borkar Roshan, Kang Sung Wook, Summers Silvia L, Putluri Vasanta, Grimm Sandra L, Venkatesh Sharan, Song Ningxin, Seeley Erin H, Hedlich-Dwyer Jenna, Chen Shu-Hsia, Mahajan Nupam P, Jain Abhinav K, Dobrolecki Lacey Elizabeth, Wells Gabrielle A, Villanueva Hugo, Li Jenny, Liu Xuefeng, Bollag Roni J, Malovannaya Anna, Jung Sung Yun, Lee Hyun-Sung, Asangani Irfan A, Terris Martha K, Creighton Chad J, Ballester Leomar Y, Karanam Balasubramanyam, Liu Suyu, Lee MinJae, Raju Rajeeva R, Siddiqui M Minhaj, Eberlin Livia S, Kommagani Ramakrishna, Sreekumar Arun, Gao Jianjun, Young Nicolas L, Hodges H Courtney, Coarfa Cristian, Gassman Natalie R, Lerner Seth P, Lotan Yair, Putluri Nagireddy. Cigarette smoke induces FASN-dependent fatty acid metabolic rewiring to drive bladder cancer progression.. Cancer letters. 2026. DOI: 10.1016/j.canlet.2026.218562.

Предметные рубрики MeSH

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

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