دورية أكاديمية
Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer.
| العنوان: | Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer. |
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| المؤلفون: | Mandigo AC; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Shafi AA; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., McCann JJ; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Yuan W; The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK., Laufer TS; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Bogdan D; The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK., Gallagher L; The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK., Dylgjeri E; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Semenova G; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Vasilevskaya IA; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Schiewer MJ; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.; Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., McNair CM; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., de Bono JS; The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK., Knudsen KE; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. karen.knudsen@jefferson.edu.; Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.; Department of Radiation Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. |
| المصدر: | Cancer research [Cancer Res] 2022 Jan 15; Vol. 82 (2), pp. 221-234. Date of Electronic Publication: 2021 Oct 08. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Carcinogenesis/*genetics , E2F1 Transcription Factor/*metabolism , Oncogene Proteins/*metabolism , Prostatic Neoplasms/*metabolism , Receptors, Androgen/*metabolism , Retinoblastoma Binding Proteins/*metabolism , Signal Transduction/*genetics , Ubiquitin-Protein Ligases/*metabolism, Apoptosis/genetics ; Binding Sites ; Cell Line, Tumor ; Cell Survival/genetics ; Cohort Studies ; E2F1 Transcription Factor/genetics ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Male ; Oncogene Proteins/genetics ; Oncogenes ; Prostatic Neoplasms/pathology ; Protein Binding/genetics ; Retinoblastoma Binding Proteins/genetics ; Transfection ; Ubiquitin-Protein Ligases/genetics |
| مستخلص: | The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling a multitude of protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment of E2F1 function after RB loss in isogenic models of prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, including the major driver of disease progression, the androgen receptor (AR). Further investigation revealed that observed AR/E2F1 cooperation elicited novel transcriptional networks that promote cancer phenotypes, especially as related to evasion of cell death. These observations were reflected in assessment of human disease, indicating the clinical relevance of the AR/E2F1 cooperome in prostate cancer. Together, these studies reveal new mechanisms by which RB loss induces cancer progression and highlight the importance of understanding the targets of E2F1 function. SIGNIFICANCE: This study identifies that RB loss in prostate cancer drives cooperation between AR and E2F1 as coregulators of transcription, which is linked to the progression of advanced disease. (©2021 The Authors; Published by the American Association for Cancer Research.) |
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| معلومات مُعتمدة: | F99 CA212225 United States CA NCI NIH HHS; P30 CA056036 United States CA NCI NIH HHS; R01 CA217329 United States CA NCI NIH HHS; T32 GM100836 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (AR protein, human) 0 (E2F1 Transcription Factor) 0 (E2F1 protein, human) 0 (Oncogene Proteins) 0 (RB1 protein, human) 0 (Receptors, Androgen) 0 (Retinoblastoma Binding Proteins) EC 2.3.2.27 (Ubiquitin-Protein Ligases) |
| تواريخ الأحداث: | Date Created: 20211009 Date Completed: 20220218 Latest Revision: 20240214 |
| رمز التحديث: | 20240214 |
| مُعرف محوري في PubMed: | PMC9397633 |
| DOI: | 10.1158/0008-5472.CAN-21-1159 |
| PMID: | 34625422 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7445 |
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| DOI: | 10.1158/0008-5472.CAN-21-1159 |