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BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis
Chen,Qiang1,2,3; Lei,Josh Haipeng1,2; Bao,Jiaolin1,2; Wang,Haitao1,2; Hao,Wenhui1,2; Li,Licen1,2; Peng,Cheng1,2; Masuda,Takaaki4; Miao,Kai1,2; Xu,Jun1,2; Xu,Xiaoling1,2; Deng,Chu Xia1,2
2020-03-01
Source PublicationAdvanced Science
ISSN2198-3844
Volume7Issue:6
Abstract

The breast cancer susceptibility gene 1 (BRCA1) is a major tumor suppressor gene and is most frequently mutated in hereditary breast cancer. BRCA1 plays a critical role in many biological processes, especially maintaining genomic stability in the nucleus, yet its role in the cytoplasm remains elusive. Here, it is revealed that BRCA1 maintains a healthy mitochondrial network through regulating mitochondrial dynamics, including fission and fusion. BRCA1 deficiency causes dysfunctional mitochondrial dynamics through increased expression of mitofusin1/2. With mitochondrial stress, BRCA1 is recruited to the mitochondrial outer membrane, where it plays an essential role in maintaining a healthy mitochondrial network. Consequently, BRCA1 deficiency impairs stress-induced mitophagy through blocking ataxia-telangiectasia mutated (ATM)-AMP-activated protein kinase (AMPK)-Dynamin-related protein 1 (DRP1)-mediated mitochondrial fission and triggers NLRP3 inflammasome activation, which creates a tumor-associated microenvironment, thereby facilitating tumor proliferation and metastasis. It is further shown that inflammasome inhibition can prevent tumor recurrence and metastasis. This study uncovers an important role of BRCA1 in regulating mitophagy and suggests a therapeutic approach for fighting this deadly disease.

KeywordAtm-ampk-drp1 Brca1 Inflammasomes Mitochondrial Dynamics Mitophagy
DOI10.1002/advs.201903616
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science
WOS SubjectChemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS IDWOS:000522170400003
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Cited Times [WOS]:17   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorChen,Qiang; Deng,Chu Xia
Affiliation1.Cancer Center,Faculty of Health Sciences,University of Macau,Macau,China
2.Center for Precision Medicine Research and Training,University of Macau,Macao
3.Zhuhai UM Science and Technology Research Institute,Zhuhai,519031,China
4.Department of Surgery,Kyushu University Beppu Hospital,Beppu-shi,874-0838,Japan
First Author AffilicationCancer Centre;  University of Macau
Corresponding Author AffilicationCancer Centre;  University of Macau
Recommended Citation
GB/T 7714
Chen,Qiang,Lei,Josh Haipeng,Bao,Jiaolin,et al. BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis[J]. Advanced Science,2020,7(6).
APA Chen,Qiang,Lei,Josh Haipeng,Bao,Jiaolin,Wang,Haitao,Hao,Wenhui,Li,Licen,Peng,Cheng,Masuda,Takaaki,Miao,Kai,Xu,Jun,Xu,Xiaoling,&Deng,Chu Xia.(2020).BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis.Advanced Science,7(6).
MLA Chen,Qiang,et al."BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis".Advanced Science 7.6(2020).
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