ArticleCancer letters2026
Cigarette smoke induces FASN-dependent fatty acid metabolic rewiring to drive bladder cancer progression.
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Article in Cancer letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
53 authors.
Chandra Sekhar AmaraDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Danthasinghe Waduge Badrajee PiyarathnaDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Abu Hena Mostafa KamalDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Advanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA.
Yuen San ChanDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX, 77030, USA.
Karthik Reddy Kami ReddyDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Chandra Shekar R AmbatiDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Advanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA.
Mohammed Khurshidul HassanDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Pratik ShriwasDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Tanmay GandhiDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Advanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA.
Antrix JainAdvanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA.
Tanja GangnusDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Pooja PopliDepartment of Pathology and Immunology, Center for Drug Discovery, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Roshan BorkarDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Sung Wook KangDepartment of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA.
Silvia L SummersVerna & Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, 77030, USA.
Vasanta PutluriDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Advanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA.
Sandra L GrimmDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Advanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA.
Sharan VenkateshDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Ningxin SongDivision of Clinical & Translational Sciences, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth Houston), Houston, TX, 77030, USA.
Erin H SeeleyDepartment of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
Jenna Hedlich-DwyerDepartment of Pathology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Shu-Hsia ChenCenter for immunotherapy, Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, 77030, USA.
Nupam P MahajanSiteman Cancer Center, Department of Surgery, Washington University in St Louis, St Louis, MO, 63110, USA.
Abhinav K JainDepartment of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Lacey Elizabeth DobroleckiAdvanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA.
Gabrielle A WellsAdvanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA.
Hugo VillanuevaAdvanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA; Department of Otolaryngology - Head and Neck Surgery, Baylor College of Medicine, Houston, TX, 77030, USA.
Jenny LiDepartment of Pathology, Wexner Medical Center, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Xuefeng LiuDepartments of Pathology, Urology, and Radiation Oncology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Roni J BollagGeorgia Cancer Center, Augusta University, Augusta, GA, 30904, USA.
Anna MalovannayaAdvanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA; Verna & Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, 77030, USA.
Sung Yun JungVerna & Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, 77030, USA.
Hyun-Sung LeeDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA.
Irfan A AsanganiDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Martha K TerrisGeorgia Cancer Center, Augusta University, Augusta, GA, 30904, USA; Department of Urology, Augusta University, Augusta, GA, 30904, USA.
Chad J CreightonDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
Leomar Y BallesterDivision of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Balasubramanyam KaranamDepartment of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL, 36088, USA.
Suyu LiuDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
MinJae LeeDivision of Clinical & Translational Sciences, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth Houston), Houston, TX, 77030, USA.
Rajeeva R RajuDepartment of Pathology, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, 44106, USA.
M Minhaj SiddiquiDivision of Urology, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Livia S EberlinDepartment of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA.
Ramakrishna KommaganiDepartment of Pathology and Immunology, Center for Drug Discovery, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Arun SreekumarDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Jianjun GaoDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Nicolas L YoungVerna & Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, 77030, USA.
H Courtney HodgesDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX, 77030, USA.
Cristian CoarfaDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Advanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA; Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX, 77030, USA.
Natalie R GassmanDepartment of Pathology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Seth P LernerDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Scott Department of Urology, Baylor College of Medicine, Houston, TX, 77030, USA.
Yair LotanDepartment of Urology, University of Texas Southwestern, Dallas, TX, 75390, USA.
Nagireddy PutluriDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA; Advanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA. Electronic address: putluri@bcm.edu.
Funding
Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI Laura Fish · 1985 to 2026
$174.8MTumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Suzanne AW Fuqua · 2007 to 2026
$73.9MUT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Kathryn Ann O'Donnell · 2010 to 2026
$53.7MProject 5: Pyolytic conversion of PAHs in contaminated sediments into char to eliminate toxicity and enhance soil fertilityP42ES027725 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI Nagireddy Putluri · 2020 to 2026
$17.8MTranslational Research Support CoreP30ES030285 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI Cheryl L. Walker · 2019 to 2026
$14.7MTMEM106b as a lysosomal adaptor to influence brain aging and tau pathogenesisP01AG066606 · NIA · BAYLOR COLLEGE OF MEDICINE · PI ZHENG, HUI · 2021 to 2025
$13.5MCirculating Biomarkers and Imaging for Early Detection of Pancreatic CancerU01CA214263 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI EUGENE J KOAY, Subrata Sen · 2018 to 2026
$7.2MCooperative Human Tissue Network Support through Duke's BioRepository & Precision Pathology CenterUM1CA239755 · NCI · DUKE UNIVERSITY · PI Shannon Jones McCall · 2019 to 2026
$5.4MMETABOLIC REGULATION IN LEUKEMIA-INITIATING CELLSR01CA193235 · NCI · BAYLOR COLLEGE OF MEDICINE · PI NAKADA, DAISUKE · 2015 to 2024
$4.6MPilot and FeasibilityP30DK144025 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Kristin Eckel Mahan · 2025 to 2026
$3.6MProteomic determinants of response to checkpoint blockade in malignant pleuralmesotheliomaR37CA248478 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Bryan Michael Burt · 2021 to 2026
$2.9MRegulation of Androgen Receptor by NXTAR Long non-coding RNA in Prostate Cancer and its Therapeutic ImplicationsR01CA285526 · NCI · WASHINGTON UNIVERSITY · PI KIRAN MAHAJAN, Nupam P Mahajan · 2024 to 2026
$2.7MNCI NIH HHS P20 CA284967NCI NIH HHS P20 CA284971NCI NIH HHS P30 CA014236NCI NIH HHS P30 CA125123NCI NIH HHS P30 CA142543NCI NIH HHS R01 CA193235NCI NIH HHS R01 CA272769NCI NIH HHS R01 CA273054NCI NIH HHS R01 CA276502NCI NIH HHS R01 CA276663NCI NIH HHS R01 CA282282NCI NIH HHS R01 CA285526NCI NIH HHS R01 CA286443NCI NIH HHS R01 CA311048NCI NIH HHS R37 CA248478NCI NIH HHS R37 CA289419NCI NIH HHS U01 CA214263NCI NIH HHS UM1 CA239755NIAID NIH HHS R21 AI159379NIA NIH HHS P01 AG066606NIA NIH HHS R01 AG074540NICHD NIH HHS R01 HD104813NICHD NIH HHS R01 HD112886NIDDK NIH HHS P30 DK144025NIEHS NIH HHS P30 ES030285NIEHS NIH HHS P42 ES027725NIGMS NIH HHS R01 GM139295NIGMS NIH HHS R01 GM141366NIH HHS S10 OD026804NIH HHS S10 OD032218NINDS NIH HHS R01 NS136375NINDS NIH HHS R01 NS137577
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.
Indexed as
Cigarette SmokingFatty AcidsFatty Acid Synthase, Type ISmokeUrinary Bladder NeoplasmsAnimalsCell Line, TumorCell ProliferationChick EmbryoDisease ProgressionDNA RepairEpigenesis, GeneticHistonesHumansMetabolic ReprogrammingFASN protein, humanFatty AcidsFatty Acid Synthase, Type IHistonesSmokeBladder cancerCigarette smokeDNA damage and repairFASNFatty acid metabolism
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