ArticleCancer cell2024
Targeting the mSWI/SNF complex in POU2F-POU2AF transcription factor-driven malignancies.
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Article in Cancer cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42citing papers in PubMed
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42 citing papers in PubMed.
- Pan-cancer analysis and mechanistic insights of tuft cell-like tumors.Genes & diseases · 2026Review
- Clonotypic characterization defines B-cell drivers of clonal expansion and intratumor heterogeneity in IgM monoclonal gammopathies.HemaSphere · 2026Article
- Integration of single-cell regulon atlas and bulk RNA-seq for individualized prognostic prediction in stomach adenocarcinoma.iScience · 2026Article
- EBNA1 inhibitors reveal CDC7 and POU2F1 as direct functional targets in EBV epithelial cancers.mBio · 2026Article
- IL-6-driven POU2AF1 and ELL2 are key regulators of multiple myeloma-distinct transcriptional and splicing programs.Blood advances · 2026Article
- Vascular STING activation facilitates NK cell anti-tumor immunity in small cell lung cancer.Cancer cell · 2026Article
- Transcription Factor Subtype Governs Response and Resistance to DLL3-Directed T-Cell Engagement in Small Cell Lung Cancer.bioRxiv : the preprint server for biology · 2026Article
- A SWI/SNF-specific Ig-like domain, SWIFT, is a transcription factor binding platform.Science (New York, N.Y.) · 2026Article
- A Double-Negative Prostate Cancer Subtype Is Vulnerable to SWI/SNF-Targeting Degrader Molecules.Cancer research · 2026Article
- Splice-site mutations in POU2AF1 are associated with B-cell lymphomagenesis and therapeutic response.Scientific reports · 2026Article
- Subtype-specific dependencies and therapeutic opportunities in small cell lung cancer.Science advances · 2026Review
- SMARCA4 Loss Promotes Late-Stage Tumor Progression in Nonneuroendocrine Small Cell Lung Cancer.Molecular cancer research : MCR · 2026Article
- Small Cell Lung Cancer Classification: Unraveling Heterogeneity to Enable Personalized Treatments.Cancer research · 2026Review
- Targeted regeneration of post-radiation epithelium without promoting cancer recurrence.Research square · 2026Article
- Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer.Journal of the National Cancer Center · 2026Review
- Tuft Cells in the Gut Limit Cognitive Disorders by Regulating Gut Homeostasis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Adjunctive diagnostic utility of POU2F3 in predominantly pulmonary high-grade neuroendocrine carcinomas with limited or discordant conventional marker expression: a case-control study.Frontiers in medicine · 2026Article
- Regulation of B cell development and lymphocyte function by transcriptional coactivator OCA-B.Frontiers in immunology · 2026Review
- Structural basis of DNA-dependent coactivator recruitment by the tuft cell master regulator POU2F3.Cell reports · 2025Article
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Authors and funding
32 authors.
Tongchen HeMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Lanbo XiaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: lanbox@med.umich.edu.
Yuanyuan QiaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Olaf KlingbeilCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Eleanor YoungMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Xiaoli S WuCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Rahul MannanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Somnath MahapatraMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Esther RedinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Hanbyul ChoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Yi BaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Malathi KandarpaRogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Jean Ching-Yi TienMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Xiaoju WangMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Sanjana EyunniMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Yang ZhengMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
NamHoon KimMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Heng ZhengMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Siyu HouDepartment of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
Fengyun SuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Stephanie J MinerMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Rohit MehraMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Xuhong CaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Chandrasekhar AbbineniAurigene Oncology Limited, Bangalore 560100, India.
Susanta SamajdarAurigene Oncology Limited, Bangalore 560100, India.
Murali RamachandraAurigene Oncology Limited, Bangalore 560100, India.
Saravana M DhanasekaranMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Moshe TalpazRogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Abhijit ParoliaMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA.
Charles M RudinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medicine Graduate School of Medicine Sciences, New York, NY 10065, USA.
Christopher R VakocCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Arul M ChinnaiyanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: arul@med.umich.edu.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MTissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Ganesh S Palapattu · 2014 to 2026
$27.6MExploring Precision Oncology: From Gene Fusions to lncRNAsR35CA231996 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M · 2018 to 2024
$6.4MExploiting POU2F3 addiction in the tuft cell variant of small cell lung cancerU01CA242919 · NCI · COLD SPRING HARBOR LABORATORY · PI VAKOC, CHRISTOPHER · 2019 to 2023
$2.2MHoward Hughes Medical InstituteNCI NIH HHS P30 CA008748NCI NIH HHS P50 CA186786NCI NIH HHS R35 CA231996NCI NIH HHS U01 CA242919
Abstract
The POU2F3-POU2AF2/3 transcription factor complex is the master regulator of the tuft cell lineage and tuft cell-like small cell lung cancer (SCLC). Here, we identify a specific dependence of the POU2F3 molecular subtype of SCLC (SCLC-P) on the activity of the mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. Treatment of SCLC-P cells with a proteolysis targeting chimera (PROTAC) degrader of mSWI/SNF ATPases evicts POU2F3 and its coactivators from chromatin and attenuates downstream signaling. B cell malignancies which are dependent on the POU2F1/2 cofactor, POU2AF1, are also sensitive to mSWI/SNF ATPase degraders, with treatment leading to chromatin eviction of POU2AF1 and IRF4 and decreased IRF4 signaling in multiple myeloma cells. An orally bioavailable mSWI/SNF ATPase degrader significantly inhibits tumor growth in preclinical models of SCLC-P and multiple myeloma without signs of toxicity. This study suggests that POU2F-POU2AF-driven malignancies have an intrinsic dependence on the mSWI/SNF complex, representing a therapeutic vulnerability.
Indexed as
Lung NeoplasmsSmall Cell Lung CarcinomaTranscription FactorsAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceOctamer Transcription Factor-2Octamer Transcription Factor-3Signal TransductionXenograft Model Antitumor AssaysOctamer Transcription Factor-2Octamer Transcription Factor-3POU2F2 protein, humanSMARCA2 protein, humanTranscription FactorsIRF4mSWI/SNF complexmultiple myelomaPOU2AF1/2/3POU2F3PROTACproteolysis targeting chimeraSCLCsmall cell lung cancerSMARCA2/4
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