Targeting CD36 determines nicotine derivative NNK-induced lung adenocarcinoma carcinogenesis
Summary: Smoking carcinogen nicotine-derived nitrosamine ketone (NNK) is the most potent contributor to lung adenocarcinoma (LUAD) development, but the mechanism has not been fully elucidated. Here, we reported that fatty acid translocase CD36 was significantly overexpressed in both human LUAD tissu...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223015547 |
| _version_ | 1797752953802588160 |
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| author | Ming-Yue Li Menghuan Wang Ming Dong Zangshu Wu Rui Zhang Bowen Wang Yuxi Huang Xiaoyang Zhang Jiaying Zhou Junbo Yi George Gong Chen Li-Zhong Liu |
| author_facet | Ming-Yue Li Menghuan Wang Ming Dong Zangshu Wu Rui Zhang Bowen Wang Yuxi Huang Xiaoyang Zhang Jiaying Zhou Junbo Yi George Gong Chen Li-Zhong Liu |
| author_sort | Ming-Yue Li |
| collection | DOAJ |
| description | Summary: Smoking carcinogen nicotine-derived nitrosamine ketone (NNK) is the most potent contributor to lung adenocarcinoma (LUAD) development, but the mechanism has not been fully elucidated. Here, we reported that fatty acid translocase CD36 was significantly overexpressed in both human LUAD tissues and NNK-induced A/J mice LUAD tumors. The overexpressed CD36 was positively correlated with Src kinase activation, smoking status, metastasis, and worse overall survival of patients with smoking history. Upon NNK binding with α7 nicotinic acetylcholine receptor (α7nAChR), sarcolemmal CD36 was increased and it interacted with surface α7nAChR and cytosol Src simultaneously, which in turn activated Src and downstream pro-carcinogenic kinase ERK1/2 and Akt, and finally caused LUAD cells to form subcutaneous and pulmonary metastatic tumors. This process could be blocked by CD36 knockdown and CD36 irreversible inhibitor SSO. Furthermore, the effect of NNK was inhibited obviously in CD36−/− A/J mice. Thus, targeting CD36 may provide a breakthrough therapy of LUAD. |
| first_indexed | 2024-03-12T17:11:53Z |
| format | Article |
| id | doaj.art-fb9f3dfd85c8498a8279ca39ca6c693a |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T17:11:53Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-fb9f3dfd85c8498a8279ca39ca6c693a2023-08-06T04:38:01ZengElsevieriScience2589-00422023-08-01268107477Targeting CD36 determines nicotine derivative NNK-induced lung adenocarcinoma carcinogenesisMing-Yue Li0Menghuan Wang1Ming Dong2Zangshu Wu3Rui Zhang4Bowen Wang5Yuxi Huang6Xiaoyang Zhang7Jiaying Zhou8Junbo Yi9George Gong Chen10Li-Zhong Liu11Department of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, Guangdong, China; GuangZhou National Laboratory, No.9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, Guangdong, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, Guangdong, China; GuangZhou National Laboratory, No.9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, Guangdong, China; GuangZhou National Laboratory, No.9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, Guangdong, China; GuangZhou National Laboratory, No.9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, Guangdong, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, Guangdong, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, Guangdong, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, Guangdong, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, Guangdong, ChinaDepartment of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, Guangdong, China; Corresponding authorSummary: Smoking carcinogen nicotine-derived nitrosamine ketone (NNK) is the most potent contributor to lung adenocarcinoma (LUAD) development, but the mechanism has not been fully elucidated. Here, we reported that fatty acid translocase CD36 was significantly overexpressed in both human LUAD tissues and NNK-induced A/J mice LUAD tumors. The overexpressed CD36 was positively correlated with Src kinase activation, smoking status, metastasis, and worse overall survival of patients with smoking history. Upon NNK binding with α7 nicotinic acetylcholine receptor (α7nAChR), sarcolemmal CD36 was increased and it interacted with surface α7nAChR and cytosol Src simultaneously, which in turn activated Src and downstream pro-carcinogenic kinase ERK1/2 and Akt, and finally caused LUAD cells to form subcutaneous and pulmonary metastatic tumors. This process could be blocked by CD36 knockdown and CD36 irreversible inhibitor SSO. Furthermore, the effect of NNK was inhibited obviously in CD36−/− A/J mice. Thus, targeting CD36 may provide a breakthrough therapy of LUAD.http://www.sciencedirect.com/science/article/pii/S2589004223015547Molecular biologyCell biologyCancer |
| spellingShingle | Ming-Yue Li Menghuan Wang Ming Dong Zangshu Wu Rui Zhang Bowen Wang Yuxi Huang Xiaoyang Zhang Jiaying Zhou Junbo Yi George Gong Chen Li-Zhong Liu Targeting CD36 determines nicotine derivative NNK-induced lung adenocarcinoma carcinogenesis iScience Molecular biology Cell biology Cancer |
| title | Targeting CD36 determines nicotine derivative NNK-induced lung adenocarcinoma carcinogenesis |
| title_full | Targeting CD36 determines nicotine derivative NNK-induced lung adenocarcinoma carcinogenesis |
| title_fullStr | Targeting CD36 determines nicotine derivative NNK-induced lung adenocarcinoma carcinogenesis |
| title_full_unstemmed | Targeting CD36 determines nicotine derivative NNK-induced lung adenocarcinoma carcinogenesis |
| title_short | Targeting CD36 determines nicotine derivative NNK-induced lung adenocarcinoma carcinogenesis |
| title_sort | targeting cd36 determines nicotine derivative nnk induced lung adenocarcinoma carcinogenesis |
| topic | Molecular biology Cell biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223015547 |
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