دورية أكاديمية
Dynamin impacts homology-directed repair and breast cancer response to chemotherapy.
العنوان: | Dynamin impacts homology-directed repair and breast cancer response to chemotherapy. |
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المؤلفون: | Chernikova SB; Department of Radiation Oncology, Stanford University, Stanford, California, USA., Nguyen RB; Department of Radiation Oncology, Stanford University, Stanford, California, USA., Truong JT; Department of Radiation Oncology, Stanford University, Stanford, California, USA., Mello SS; Department of Radiation Oncology, Stanford University, Stanford, California, USA., Stafford JH; Department of Radiation Oncology, Stanford University, Stanford, California, USA., Hay MP; Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand., Olson A; Microscopy Service., Solow-Cordero DE; High-Throughput Bioscience Center., Wood DJ; Data Coordinating Center, Department of Biomedical Data Science, and., Henry S; Data Coordinating Center, Department of Biomedical Data Science, and., von Eyben R; Department of Radiation Oncology, Stanford University, Stanford, California, USA., Deng L; Department of Radiation Oncology, Stanford University, Stanford, California, USA., Gephart MH; Department of Neurosurgery, Stanford University, Stanford, California, USA., Aroumougame A; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Wiese C; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado, USA., Game JC; Department of Radiation Oncology, Stanford University, Stanford, California, USA., Győrffy B; MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Budapest, Hungary.; Semmelweis University 2nd Department of Pediatrics, Budapest, Hungary., Brown JM; Department of Radiation Oncology, Stanford University, Stanford, California, USA. |
المصدر: | The Journal of clinical investigation [J Clin Invest] 2018 Dec 03; Vol. 128 (12), pp. 5307-5321. Date of Electronic Publication: 2018 Oct 29. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation Original Publication: New Haven [etc.] American Society for Clinical Investigation. |
مواضيع طبية MeSH: | Recombinational DNA Repair*, Antineoplastic Agents/*pharmacology , Dynamins/*metabolism , Triple Negative Breast Neoplasms/*drug therapy , Triple Negative Breast Neoplasms/*enzymology, Animals ; CHO Cells ; Cricetulus ; Dynamin II ; Dynamins/genetics ; Female ; Humans ; Mice ; Mice, Nude ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/pathology ; Xenograft Model Antitumor Assays |
مستخلص: | After the initial responsiveness of triple-negative breast cancers (TNBCs) to chemotherapy, they often recur as chemotherapy-resistant tumors, and this has been associated with upregulated homology-directed repair (HDR). Thus, inhibitors of HDR could be a useful adjunct to chemotherapy treatment of these cancers. We performed a high-throughput chemical screen for inhibitors of HDR from which we obtained a number of hits that disrupted microtubule dynamics. We postulated that high levels of the target molecules of our screen in tumors would correlate with poor chemotherapy response. We found that inhibition or knockdown of dynamin 2 (DNM2), known for its role in endocytic cell trafficking and microtubule dynamics, impaired HDR and improved response to chemotherapy of cells and of tumors in mice. In a retrospective analysis, levels of DNM2 at the time of treatment strongly predicted chemotherapy outcome for estrogen receptor-negative and especially for TNBC patients. We propose that DNM2-associated DNA repair enzyme trafficking is important for HDR efficiency and is a powerful predictor of sensitivity to breast cancer chemotherapy and an important target for therapy. |
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معلومات مُعتمدة: | P01 CA067166 United States CA NCI NIH HHS; P30 NS069375 United States NS NINDS NIH HHS; R01 ES021454 United States ES NIEHS NIH HHS; UL1 RR025744 United States RR NCRR NIH HHS; R01 AG053341 United States AG NIA NIH HHS; K08 NS091527 United States NS NINDS NIH HHS; P30 CA124435 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: Breast cancer; DNA repair; Oncology |
المشرفين على المادة: | 0 (Antineoplastic Agents) EC 3.6.5.5 (DNM2 protein, human) EC 3.6.5.5 (Dynamin II) EC 3.6.5.5 (Dynamins) |
تواريخ الأحداث: | Date Created: 20181030 Date Completed: 20190916 Latest Revision: 20210821 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC6264728 |
DOI: | 10.1172/JCI87191 |
PMID: | 30371505 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1558-8238 |
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DOI: | 10.1172/JCI87191 |