دورية أكاديمية
أعرض في EDS

Genome-wide CRISPR screen reveals the synthetic lethality between BCL2L1 inhibition and radiotherapy.

التفاصيل البيبلوغرافية
العنوان: Genome-wide CRISPR screen reveals the synthetic lethality between BCL2L1 inhibition and radiotherapy.
المؤلفون: Yin L; https://ror.org/04twxam07 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hu X; https://ror.org/04twxam07 Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; https://ror.org/04twxam07 Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Pei G; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA., Tang M; https://ror.org/04twxam07 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhou Y; https://ror.org/04twxam07 Department of Pediatrics Research, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhang H; https://ror.org/04twxam07 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Huang M; https://ror.org/04twxam07 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Li S; https://ror.org/04twxam07 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhang J; https://ror.org/04twxam07 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Citu C; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA., Zhao Z; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA., Debeb BG; https://ror.org/04twxam07 Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; https://ror.org/04twxam07 Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Feng X; https://ror.org/04twxam07 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA fengxu@njmu.edu.cn.; Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.; Pancreas Institute, Nanjing Medical University, Nanjing, China., Chen J; https://ror.org/04twxam07 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA JChen8@mdanderson.org.
المصدر: Life science alliance [Life Sci Alliance] 2024 Feb 05; Vol. 7 (4). Date of Electronic Publication: 2024 Feb 05 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Life Science Alliance, LLC Country of Publication: United States NLM ID: 101728869 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2575-1077 (Electronic) Linking ISSN: 25751077 NLM ISO Abbreviation: Life Sci Alliance Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Woodbury, NY] : Life Science Alliance, LLC, [2018]-
مواضيع طبية MeSH: bcl-X Protein*/genetics , bcl-X Protein*/metabolism , Breast Neoplasms*/genetics , Breast Neoplasms*/radiotherapy , Breast Neoplasms*/metabolism , Synthetic Lethal Mutations*/genetics, Female ; Humans ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; NF-kappa B/genetics ; NF-kappa B/metabolism
مستخلص: Radiation therapy (RT) is one of the most commonly used anticancer therapies. However, the landscape of cellular response to irradiation, especially to a single high-dose irradiation, remains largely unknown. In this study, we performed a whole-genome CRISPR loss-of-function screen and revealed temporal inherent and acquired responses to RT. Specifically, we found that loss of the IL1R1 pathway led to cellular resistance to RT. This is in part because of the involvement of radiation-induced IL1R1-dependent transcriptional regulation, which relies on the NF-κB pathway. Moreover, the mitochondrial anti-apoptotic pathway, particularly the BCL2L1 gene, is crucially important for cell survival after radiation. BCL2L1 inhibition combined with RT dramatically impeded tumor growth in several breast cancer cell lines and syngeneic models. Taken together, our results suggest that the combination of an apoptosis inhibitor such as a BCL2L1 inhibitor with RT may represent a promising anticancer strategy for solid cancers including breast cancer.
(© 2024 Yin et al.)
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معلومات مُعتمدة: R01 CA210929 United States CA NCI NIH HHS; R01 CA275712 United States CA NCI NIH HHS; R35 CA274234 United States CA NCI NIH HHS; R01 CA216437 United States CA NCI NIH HHS; R01 CA216911 United States CA NCI NIH HHS; P01 CA193124 United States CA NCI NIH HHS
المشرفين على المادة: 0 (bcl-X Protein)
0 (BCL2L1 protein, human)
0 (NF-kappa B)
تواريخ الأحداث: Date Created: 20240205 Date Completed: 20240207 Latest Revision: 20240308
رمز التحديث: 20240309
مُعرف محوري في PubMed: PMC10844523
DOI: 10.26508/lsa.202302353
PMID: 38316463
قاعدة البيانات: MEDLINE
الوصف
تدمد:2575-1077
DOI:10.26508/lsa.202302353