دورية أكاديمية
SMARCA4 biology in alveolar rhabdomyosarcoma.
العنوان: | SMARCA4 biology in alveolar rhabdomyosarcoma. |
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المؤلفون: | Bharathy N; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA.; Gene Therapy Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Cleary MM; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Kim JA; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Nagamori K; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Crawford KA; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Wang E; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA., Saha D; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA.; CSIR-CCMB, Uppal Road, Hyderabad, 500007, India., Settelmeyer TP; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Purohit R; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Skopelitis D; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA., Chang K; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA., Doran JA; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Kirschbaum CW; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Bharathy S; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Crews DW; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Randolph ME; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Karnezis AN; University of California C Davis Medical Center, Sacramento, CA, 95817, USA.; British Columbia Cancer Research Center, Vancouver, BC, V5Z 1L3, Canada., Hudson-Price L; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA., Dhawan J; CSIR-CCMB, Uppal Road, Hyderabad, 500007, India., Michalek JE; Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio, TX, 78229, USA., Ciulli A; Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK. a.ciulli@dundee.ac.uk., Vakoc CR; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA., Keller C; Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA. charles@cc-tdi.org. |
المصدر: | Oncogene [Oncogene] 2022 Mar; Vol. 41 (11), pp. 1647-1656. Date of Electronic Publication: 2022 Jan 29. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <2002->: Basingstoke : Nature Publishing Group Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987- |
مواضيع طبية MeSH: | Neoplasms* , Rhabdomyosarcoma, Alveolar*/genetics , Rhabdomyosarcoma, Embryonal*, Biology ; Child ; DNA Helicases/genetics ; Humans ; Nuclear Proteins/genetics ; Transcription Factors/genetics |
مستخلص: | Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and phenocopies a muscle precursor that fails to undergo terminal differentiation. The alveolar subtype (ARMS) has the poorest prognosis and represents the greatest unmet medical need for RMS. Emerging evidence supports the role of epigenetic dysregulation in RMS. Here we show that SMARCA4/BRG1, an ATP-dependent chromatin remodeling enzyme of the SWI/SNF complex, is prominently expressed in primary tumors from ARMS patients and cell cultures. Our validation studies for a CRISPR screen of 400 epigenetic targets identified SMARCA4 as a unique factor for long-term (but not short-term) tumor cell survival in ARMS. A SMARCA4/SMARCA2 protein degrader (ACBI-1) demonstrated similar long-term tumor cell dependence in vitro and in vivo. These results credential SMARCA4 as a tumor cell dependency factor and a therapeutic target in ARMS. (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.) |
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معلومات مُعتمدة: | R01 CA189299 United States CA NCI NIH HHS; R21 CA245859 United States CA NCI NIH HHS; P30 CA045508 United States CA NCI NIH HHS; P01 CA013106 United States CA NCI NIH HHS; R01 CA258720 United States CA NCI NIH HHS |
المشرفين على المادة: | 0 (Nuclear Proteins) 0 (Transcription Factors) EC 3.6.1.- (SMARCA4 protein, human) EC 3.6.4.- (DNA Helicases) |
تواريخ الأحداث: | Date Created: 20220130 Date Completed: 20220419 Latest Revision: 20240607 |
رمز التحديث: | 20240607 |
مُعرف محوري في PubMed: | PMC9985831 |
DOI: | 10.1038/s41388-022-02205-0 |
PMID: | 35094009 |
قاعدة البيانات: | MEDLINE |
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