ArticleNature communications2024
The IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer.
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30 citing papers in PubMed, 32 citations in OpenAlex.
- Sphingosine-1-phosphate induces angiogenesis via the activating STAT3 signaling pathway to drive colorectal cancer progression.Journal of gastrointestinal oncology · 2026Article
- Cigarette smoke induces FASN-dependent fatty acid metabolic rewiring to drive bladder cancer progression.Cancer letters · 2026Article
- Blockage of cuproplasia inhibits pancreatic tumour-associated neutrophils infiltration through TRAF6/STAT3/CCL2 pathway.British journal of cancer · 2026Article
- Targeting EZH2-driven cholesterol metabolic vulnerability through Napabucasin suppresses ovarian cancer metastasis.Cell death & disease · 2026Article
- Leveraging untargeted metabolomics in combination with machine learning to uncover novel insights into bladder cancer.Cancer & metabolism · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Integration of bulk and single-cell transcriptomic sequencing reveals the neutrophil heterogeneity in bladder cancer and establishes a prognostic model.Discover oncology · 2026Article
- Integrative single-cell and machine learning framework reveals prognostic fibroblast subtypes and constructs a fibroblast-related risk signature in lung adenocarcinoma.Scientific reports · 2026Article
- Crucial Contribution of BACH1 to Bladder Cancer Progression via Upregulating Epithelial-Mesenchymal Transition Pathway.Cancer science · 2026Article
- ARID1A deficiency activates OSM-STAT3 axis in endometrial cancer, creating vulnerability to JAK/STAT3 inhibition.International journal of biological sciences · 2026Article
- Alantolactone curbs the malignant progression of bladder cancer partly via the HSP90AB1/LRP5/β-catenin axis.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- ERO1A-positive tumor epithelial cells in colorectal cancer progression: a multi-omics perspective.Apoptosis : an international journal on programmed cell death · 2025Article
- Construction of a gene-metabolite-microbiome regulatory network reveals novel therapeutic targets in bladder cancer through multi-omics analysis.Annals of medicine · 2025Article
- EGFR-STAT3 activation provides a therapeutic rationale for targeting aggressive ETV1-positive prostate cancer.Molecular oncology · 2025Article
- Screening of PANoptosis regulator-associated long noncoding RNAs and construction of a survival prognostic model in cutaneous melanoma.Translational cancer research · 2025Article
- Integrating single-cell RNA sequencing and spatial transcriptomics reveals the therapeutic effect of nitazoxanide in head and neck squamous cell carcinoma.Discover oncology · 2025Article
- IL-6 predicts CDK4/6 inhibitor resistance, identifying STAT3 as a target in HR + /HER2-negative metastatic breast cancer.NPJ precision oncology · 2025Article
- Repurposing Amiodarone for Bladder Cancer Treatment.Cancer research communications · 2025Article
- The key regulator circPDE3B promotes arsenic-induced bladder carcinogenesis by affecting STAT3 and NF-κB stability.Cell biology and toxicology · 2025Article
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Authors and funding
24 authors at 5 institutions in 1 country.
Chandra Sekhar AmaraDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.ORCID 0000-0002-8256-7291
Karthik Reddy Kami Reddy *Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Yang Yuntao *Mcwilliams School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Yuen San ChanDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Danthasinghe Waduge Badrajee PiyarathnaDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Lacey Elizabeth DobroleckiAdvanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA.ORCID 0000-0001-6839-629X
David J H ShihMcwilliams School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.ORCID 0000-0002-9802-4937
Zhongcheng ShiAdvanced Technology Cores, Baylor College of Medicine, Houston, TX, 77030, USA.
Jun XuDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Shixia HuangDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Matthew J EllisLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Andrea B ApoloGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID 0000-0001-9409-1836
Leomar Y BallesterDivision of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Jianjun GaoDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID 0000-0001-6138-4472
Donna E HanselDivision of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Yair LotanDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID 0000-0001-5692-2723
H Courtney HodgesDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.ORCID 0000-0003-4441-497X
Seth P LernerScott Department of Urology, Baylor College of Medicine, Houston, TX, 77030, USA.ORCID 0000-0002-6379-2581
Chad J CreightonDan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.ORCID 0000-0002-6090-703X
Arun SreekumarDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
W Jim ZhengMcwilliams School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.ORCID 0000-0001-7411-6047
Pavlos MsaouelDepartment of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. pmsaouel@mdanderson.org.ORCID 0000-0001-6505-8308
Shyam M KavuriLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA. meghashyam.kavuri@bcm.edu.ORCID 0000-0002-3321-6727
Nagireddy PutluriDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA. putluri@bcm.edu.ORCID 0000-0003-4488-7400
Baylor College of Medicine · USThe University of Texas MD Anderson Cancer Center · USThe University of Texas Health Science Center at Houston · USNational Institutes of Health · USThe University of Texas Southwestern Medical Center · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MTumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9MUT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MELANIE H. COBB · 2010 to 2026
$53.7MConvalescent Plasma to Limit Coronavirus Associated ComplicationsUL1TR003167 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KARP, DANIEL D, MCPHERSON, DAVID D · 2019 to 2023
$45.3MProject 5: Pyolytic conversion of PAHs in contaminated sediments into char to eliminate toxicity and enhance soil fertilityP42ES027725 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI BHAGAVATULA MOORTHY · 2020 to 2026
$17.8MEffective combination therapy for MTAP-deficient bladder carcinoma by targeting metabolic vulnerability and modulating tumor immune microenvironmentR01CA254988 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GAO, JIANJUN · 2021 to 2025
$2.6MDecoding tumor metabolic and immunologic interactions driving racial disparity in African American patients with bladder cancer.R01CA282282 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Jianjun Gao, Nagireddy Putluri · 2023 to 2026
$2.5MMechanisms and small-molecule targeting of SWI/SNF activity in neuroblastomaR01CA272769 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Hamilton Courtney Hodges · 2022 to 2026
$2.3MIdentify the DNA Adduct and Associated Metabolic Alterations in Bladder Cancer of SmokersR01CA216426 · NCI · BAYLOR COLLEGE OF MEDICINE · PI EL-ZEIN, RANDA A, PUTLURI, NAGIREDDY · 2018 to 2022
$2.0MRacial Disparity in Bladder Cancer and Identification of Altered Metabolism in African American Compare to European Bladder CancerR01CA220297 · NCI · BAYLOR COLLEGE OF MEDICINE · PI PUTLURI, NAGIREDDY · 2017 to 2021
$1.8MRacial and social contextual factors in relation to epigenome and bladder cancer outcome.P20CA284971 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Rayne Helen Rouce · 2023 to 2026
$1.4MRacial and social contextual factors in relation to epigenome and bladder cancer outcomeP20CA284967 · NCI · TEXAS SOUTHERN UNIVERSITY · PI Dong Liang · 2023 to 2026
$1.3MNCATS NIH HHS UL1 TR003167NCI NIH HHS P20 CA284967NCI NIH HHS P20 CA284971NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA125123NCI NIH HHS P30 CA142543NCI NIH HHS R01 CA216426NCI NIH HHS R01 CA220297NCI NIH HHS R01 CA254988NCI NIH HHS R01 CA272769NCI NIH HHS R01 CA282282NIEHS NIH HHS P42 ES027725NIH HHS S10 OD028648
Abstract
SMARCB1 loss has long been observed in many solid tumors. However, there is a need to elucidate targetable pathways driving growth and metastasis in SMARCB1-deficient tumors. Here, we demonstrate that SMARCB1 deficiency, defined as genomic SMARCB1 copy number loss associated with reduced mRNA, drives disease progression in patients with bladder cancer by engaging STAT3. SMARCB1 loss increases the chromatin accessibility of the STAT3 locus in vitro. Orthotopically implanted SMARCB1 knockout (KO) cell lines exhibit increased tumor growth and metastasis. SMARCB1-deficient tumors show an increased IL6/JAK/STAT3 signaling axis in in vivo models and patients. Furthermore, a pSTAT3 selective inhibitor, TTI-101, reduces tumor growth in SMARCB1 KO orthotopic cell line-derived xenografts and a SMARCB1-deficient patient derived xenograft model. We have identified a gene signature generated from SMARCB1 KO tumors that predicts SMARCB1 deficiency in patients. Overall, these findings support the clinical evaluation of STAT3 inhibitors for the treatment of SMARCB1-deficient bladder cancer.
Indexed as
Interleukin-6Urinary Bladder NeoplasmsCell Line, TumorHumansSignal TransductionSMARCB1 ProteinSTAT3 Transcription FactorInterleukin-6SMARCB1 ProteinSMARCB1 protein, humanSTAT3 protein, humanSTAT3 Transcription Factor
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