Systematic identification of CDC34 that functions to stabilize EGFR and promote lung carcinogenesis
Identifieur interne : 000042 ( Main/Exploration ); précédent : 000041; suivant : 000043Systematic identification of CDC34 that functions to stabilize EGFR and promote lung carcinogenesis
Auteurs : Xin-Chun Zhao [République populaire de Chine] ; Gui-Zhen Wang [République populaire de Chine] ; Zhe-Sheng Wen [République populaire de Chine] ; Yong-Chun Zhou [République populaire de Chine] ; Qian Hu [République populaire de Chine] ; Bin Zhang [République populaire de Chine] ; Li-Wei Qu [République populaire de Chine] ; San-Hui Gao [République populaire de Chine] ; Jie Liu [République populaire de Chine] ; Liang Ma [République populaire de Chine] ; Yan-Fei Zhang [République populaire de Chine] ; Chen Zhang [République populaire de Chine] ; Hong Yu [République populaire de Chine] ; Da-Lin Zhang [République populaire de Chine] ; Min Wang [République populaire de Chine] ; Chang-Li Wang [République populaire de Chine] ; Yun-Chao Huang [République populaire de Chine] ; Zhi-Hua Liu [République populaire de Chine] ; Yong Zhao [République populaire de Chine] ; Liang Chen [République populaire de Chine] ; Guang-Biao Zhou [République populaire de Chine]Source :
- EBioMedicine [ 2352-3964 ] ; 2020.
Abstract
How the oncoprotein epidermal growth factor receptor (EGFR) evades proteolytic degradation and accumulates in non-small cell lung cancer (NSCLC) remains unclear, and ubiquitin pathway genes (UPGs) that are critical to NSCLC needs to be systematically identified.
A total of 696 UPGs (including E1, E2, E3, and deubiquitinases) were silenced by small interfering RNA (siRNA) library in NSCLC cells, the candidates were verified, and their significance was evaluated in patients with NSCLC. The effects of a candidate gene on EGFR were investigated
We report 31 candidates that are required for cell proliferation, with the E2 ubiquitin conjugase CDC34 as the most significant one. CDC34 is elevated in tumor tissues in 76 of 114 (66.7%) NSCLCs and inversely associated with prognosis, is higher in smoker patients than nonsmoker patients, and is induced by tobacco carcinogens in normal human lung epithelial cells. Forced expression of CDC34 promotes, whereas knockdown of CDC34 inhibits, NSCLC cell proliferation
These results demonstrate that an E2 enzyme is capable of competing with E3 ligase to stabilize substrates, and CDC34 represents an attractive therapeutic target for NSCLCs.
National Key Research and Development Program of China, National Natural Science Foundation of China, and the CAMS Innovation Fund for Medical Sciences.
Url:
DOI: 10.1016/j.ebiom.2020.102689
PubMed: 32114396
PubMed Central: 7047192
Affiliations:
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wicri:level="1"><nlm:aff id="aff0001">State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0006">School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Beijing 100029, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Beijing 100029</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Da Lin" sort="Zhang, Da Lin" uniqKey="Zhang D" first="Da-Lin" last="Zhang">Da-Lin Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wang, Min" sort="Wang, Min" uniqKey="Wang M" first="Min" last="Wang">Min Wang</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wang, Chang Li" sort="Wang, Chang Li" uniqKey="Wang C" first="Chang-Li" last="Wang">Chang-Li Wang</name><affiliation wicri:level="1"><nlm:aff id="aff0007">Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Huang, Yun Chao" sort="Huang, Yun Chao" uniqKey="Huang Y" first="Yun-Chao" last="Huang">Yun-Chao Huang</name><affiliation wicri:level="1"><nlm:aff id="aff0005">Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University, Kunming 650106, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University, Kunming 650106</wicri:regionArea><wicri:noRegion>Kunming 650106</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Zhi Hua" sort="Liu, Zhi Hua" uniqKey="Liu Z" first="Zhi-Hua" last="Liu">Zhi-Hua Liu</name><affiliation wicri:level="1"><nlm:aff id="aff0001">State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhao, Yong" sort="Zhao, Yong" uniqKey="Zhao Y" first="Yong" last="Zhao">Yong Zhao</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Chen, Liang" sort="Chen, Liang" uniqKey="Chen L" first="Liang" last="Chen">Liang Chen</name><affiliation wicri:level="1"><nlm:aff id="aff0008">Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Life and Health Engineering, Jinan University, Guangzhou 510632</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Zhou, Guang Biao" sort="Zhou, Guang Biao" uniqKey="Zhou G" first="Guang-Biao" last="Zhou">Guang-Biao Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff0001">State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32114396</idno><idno type="pmc">7047192</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047192</idno><idno type="RBID">PMC:7047192</idno><idno type="doi">10.1016/j.ebiom.2020.102689</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000506</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000506</idno><idno type="wicri:Area/Pmc/Curation">000506</idno><idno 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for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0003">Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou 221002, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou 221002</wicri:regionArea><wicri:noRegion>Xuzhou 221002</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Gui Zhen" sort="Wang, Gui Zhen" uniqKey="Wang G" first="Gui-Zhen" last="Wang">Gui-Zhen Wang</name><affiliation wicri:level="1"><nlm:aff id="aff0001">State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wen, Zhe Sheng" sort="Wen, Zhe Sheng" uniqKey="Wen Z" first="Zhe-Sheng" last="Wen">Zhe-Sheng Wen</name><affiliation wicri:level="1"><nlm:aff id="aff0004">State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Medical Oncology Department, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Medical Oncology Department, Sun Yat-Sen University Cancer Center, Guangzhou, 510060</wicri:regionArea><wicri:noRegion>510060</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Yong Chun" sort="Zhou, Yong Chun" uniqKey="Zhou Y" first="Yong-Chun" last="Zhou">Yong-Chun Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff0005">Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University, Kunming 650106, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University, Kunming 650106</wicri:regionArea><wicri:noRegion>Kunming 650106</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Qian" sort="Hu, Qian" uniqKey="Hu Q" first="Qian" last="Hu">Qian Hu</name><affiliation wicri:level="1"><nlm:aff id="aff0001">State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0006">School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Beijing 100029, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Beijing 100029</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Bin" sort="Zhang, Bin" uniqKey="Zhang B" first="Bin" last="Zhang">Bin Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff0007">Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Qu, Li Wei" sort="Qu, Li Wei" uniqKey="Qu L" first="Li-Wei" last="Qu">Li-Wei Qu</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Gao, San Hui" sort="Gao, San Hui" uniqKey="Gao S" first="San-Hui" last="Gao">San-Hui Gao</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Liu, Jie" sort="Liu, Jie" uniqKey="Liu J" first="Jie" last="Liu">Jie Liu</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Ma, Liang" sort="Ma, Liang" uniqKey="Ma L" first="Liang" last="Ma">Liang Ma</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Yan Fei" sort="Zhang, Yan Fei" uniqKey="Zhang Y" first="Yan-Fei" last="Zhang">Yan-Fei Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Chen" sort="Zhang, Chen" uniqKey="Zhang C" first="Chen" last="Zhang">Chen Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Yu, Hong" sort="Yu, Hong" uniqKey="Yu H" first="Hong" last="Yu">Hong Yu</name><affiliation wicri:level="1"><nlm:aff id="aff0001">State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0006">School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Beijing 100029, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Beijing 100029</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Da Lin" sort="Zhang, Da Lin" uniqKey="Zhang D" first="Da-Lin" last="Zhang">Da-Lin Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wang, Min" sort="Wang, Min" uniqKey="Wang M" first="Min" last="Wang">Min Wang</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wang, Chang Li" sort="Wang, Chang Li" uniqKey="Wang C" first="Chang-Li" last="Wang">Chang-Li Wang</name><affiliation wicri:level="1"><nlm:aff id="aff0007">Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Huang, Yun Chao" sort="Huang, Yun Chao" uniqKey="Huang Y" first="Yun-Chao" last="Huang">Yun-Chao Huang</name><affiliation wicri:level="1"><nlm:aff id="aff0005">Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University, Kunming 650106, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University, Kunming 650106</wicri:regionArea><wicri:noRegion>Kunming 650106</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Zhi Hua" sort="Liu, Zhi Hua" uniqKey="Liu Z" first="Zhi-Hua" last="Liu">Zhi-Hua Liu</name><affiliation wicri:level="1"><nlm:aff id="aff0001">State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhao, Yong" sort="Zhao, Yong" uniqKey="Zhao Y" first="Yong" last="Zhao">Yong Zhao</name><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Chen, Liang" sort="Chen, Liang" uniqKey="Chen L" first="Liang" last="Chen">Liang Chen</name><affiliation wicri:level="1"><nlm:aff id="aff0008">Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Life and Health Engineering, Jinan University, Guangzhou 510632</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Zhou, Guang Biao" sort="Zhou, Guang Biao" uniqKey="Zhou G" first="Guang-Biao" last="Zhou">Guang-Biao Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff0001">State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0002">State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author></analytic><series><title level="j">EBioMedicine</title><idno type="eISSN">2352-3964</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>How the oncoprotein epidermal growth factor receptor (EGFR) evades proteolytic degradation and accumulates in non-small cell lung cancer (NSCLC) remains unclear, and ubiquitin pathway genes (UPGs) that are critical to NSCLC needs to be systematically identified.</p></sec><sec><title>Methods</title><p>A total of 696 UPGs (including E1, E2, E3, and deubiquitinases) were silenced by small interfering RNA (siRNA) library in NSCLC cells, the candidates were verified, and their significance was evaluated in patients with NSCLC. The effects of a candidate gene on EGFR were investigated <italic>in vitro</italic> and <italic>in vivo</italic>.</p></sec><sec><title>Findings</title><p>We report 31 candidates that are required for cell proliferation, with the E2 ubiquitin conjugase CDC34 as the most significant one. CDC34 is elevated in tumor tissues in 76 of 114 (66.7%) NSCLCs and inversely associated with prognosis, is higher in smoker patients than nonsmoker patients, and is induced by tobacco carcinogens in normal human lung epithelial cells. Forced expression of CDC34 promotes, whereas knockdown of CDC34 inhibits, NSCLC cell proliferation <italic>in vitro</italic> and <italic>in vivo</italic>. CDC34 competes with c-Cbl to bind Y1045 to inhibit polyubiquitination and degradation of EGFR. In EGFR-L858R and EGFR-T790M/Del (exon 19)-driven lung tumor growth in mouse models, knockdown of CDC34 significantly inhibits tumor formation.</p></sec><sec><title>Interpretation</title><p>These results demonstrate that an E2 enzyme is capable of competing with E3 ligase to stabilize substrates, and CDC34 represents an attractive therapeutic target for NSCLCs.</p></sec><sec><title>Funding</title><p>National Key Research and Development Program of China, National Natural Science Foundation of China, and the CAMS Innovation Fund for Medical Sciences.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Cataldo, V D" uniqKey="Cataldo V">V.D. Cataldo</name></author><author><name sortKey="Gibbons, D L" uniqKey="Gibbons D">D.L. Gibbons</name></author><author><name sortKey="Perez Soler, R" uniqKey="Perez Soler R">R. Perez-Soler</name></author><author><name sortKey="Quintas Cardama, A" uniqKey="Quintas Cardama A">A. 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Capelletti</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Guangdong</li></region><settlement><li>Jiangmen</li><li>Pékin</li><li>Tianjin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Zhao, Xin Chun" sort="Zhao, Xin Chun" uniqKey="Zhao X" first="Xin-Chun" last="Zhao">Xin-Chun Zhao</name></noRegion><name sortKey="Chen, Liang" sort="Chen, Liang" uniqKey="Chen L" first="Liang" last="Chen">Liang Chen</name><name sortKey="Gao, San Hui" sort="Gao, San Hui" uniqKey="Gao S" first="San-Hui" last="Gao">San-Hui Gao</name><name sortKey="Hu, Qian" sort="Hu, Qian" uniqKey="Hu Q" first="Qian" last="Hu">Qian Hu</name><name sortKey="Hu, Qian" sort="Hu, Qian" uniqKey="Hu Q" first="Qian" last="Hu">Qian Hu</name><name sortKey="Huang, Yun Chao" sort="Huang, Yun Chao" uniqKey="Huang Y" first="Yun-Chao" last="Huang">Yun-Chao Huang</name><name sortKey="Liu, Jie" sort="Liu, Jie" uniqKey="Liu J" first="Jie" last="Liu">Jie Liu</name><name sortKey="Liu, Zhi Hua" sort="Liu, Zhi Hua" uniqKey="Liu Z" first="Zhi-Hua" last="Liu">Zhi-Hua Liu</name><name sortKey="Ma, Liang" sort="Ma, Liang" uniqKey="Ma L" first="Liang" last="Ma">Liang Ma</name><name sortKey="Qu, Li Wei" sort="Qu, Li Wei" uniqKey="Qu L" first="Li-Wei" last="Qu">Li-Wei Qu</name><name sortKey="Wang, Chang Li" sort="Wang, Chang Li" uniqKey="Wang C" first="Chang-Li" last="Wang">Chang-Li Wang</name><name sortKey="Wang, Gui Zhen" sort="Wang, Gui Zhen" uniqKey="Wang G" first="Gui-Zhen" last="Wang">Gui-Zhen Wang</name><name sortKey="Wang, Gui Zhen" sort="Wang, Gui Zhen" uniqKey="Wang G" first="Gui-Zhen" last="Wang">Gui-Zhen Wang</name><name sortKey="Wang, Min" sort="Wang, Min" uniqKey="Wang M" first="Min" last="Wang">Min Wang</name><name sortKey="Wen, Zhe Sheng" sort="Wen, Zhe Sheng" uniqKey="Wen Z" first="Zhe-Sheng" last="Wen">Zhe-Sheng Wen</name><name sortKey="Yu, Hong" sort="Yu, Hong" uniqKey="Yu H" first="Hong" last="Yu">Hong Yu</name><name sortKey="Yu, Hong" sort="Yu, Hong" uniqKey="Yu H" first="Hong" last="Yu">Hong Yu</name><name sortKey="Zhang, Bin" sort="Zhang, Bin" uniqKey="Zhang B" first="Bin" last="Zhang">Bin Zhang</name><name sortKey="Zhang, Chen" sort="Zhang, Chen" uniqKey="Zhang C" first="Chen" last="Zhang">Chen Zhang</name><name sortKey="Zhang, Da Lin" sort="Zhang, Da Lin" uniqKey="Zhang D" first="Da-Lin" last="Zhang">Da-Lin Zhang</name><name sortKey="Zhang, Yan Fei" sort="Zhang, Yan Fei" uniqKey="Zhang Y" first="Yan-Fei" last="Zhang">Yan-Fei Zhang</name><name sortKey="Zhao, Xin Chun" sort="Zhao, Xin Chun" uniqKey="Zhao X" first="Xin-Chun" last="Zhao">Xin-Chun Zhao</name><name sortKey="Zhao, Xin Chun" sort="Zhao, Xin Chun" uniqKey="Zhao X" first="Xin-Chun" last="Zhao">Xin-Chun Zhao</name><name sortKey="Zhao, Yong" sort="Zhao, Yong" uniqKey="Zhao Y" first="Yong" last="Zhao">Yong Zhao</name><name sortKey="Zhou, Guang Biao" sort="Zhou, Guang Biao" uniqKey="Zhou G" first="Guang-Biao" last="Zhou">Guang-Biao Zhou</name><name sortKey="Zhou, Guang Biao" sort="Zhou, Guang Biao" uniqKey="Zhou G" first="Guang-Biao" last="Zhou">Guang-Biao Zhou</name><name sortKey="Zhou, Yong Chun" sort="Zhou, Yong Chun" uniqKey="Zhou Y" first="Yong-Chun" last="Zhou">Yong-Chun Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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