TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis
Abstract Mitochondrial function and homeostasis are critical to the proliferation of lung cancer cells. T-cell immunoglobulin and mucin domain-containing molecule 4 (TIM-4) promotes the development and progression of lung cancer. However, the role of TIM-4 in mitochondria homeostasis in tumor cells...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-02-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05678-3 |
| _version_ | 1797863395077128192 |
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| author | Yuzhen Wang Yingchun Wang Wen Liu Lu Ding Xiaodi Zhang Bo Wang Zheng Tong Xuetian Yue Chunyang Li Liyun Xu Zhuanchang Wu Xiaohong Liang Chunhong Ma Lifen Gao |
| author_facet | Yuzhen Wang Yingchun Wang Wen Liu Lu Ding Xiaodi Zhang Bo Wang Zheng Tong Xuetian Yue Chunyang Li Liyun Xu Zhuanchang Wu Xiaohong Liang Chunhong Ma Lifen Gao |
| author_sort | Yuzhen Wang |
| collection | DOAJ |
| description | Abstract Mitochondrial function and homeostasis are critical to the proliferation of lung cancer cells. T-cell immunoglobulin and mucin domain-containing molecule 4 (TIM-4) promotes the development and progression of lung cancer. However, the role of TIM-4 in mitochondria homeostasis in tumor cells remains completely unknown. In this study, we found that TIM-4 promoted growth and proliferation of lung cancer cells by the oxidative phosphorylation (OXPHOS) pathway. Consistently, inhibition of OXPHOS reversed TIM-4-induced proliferation of lung cancer cells. Notably, TIM-4 promoted mitochondrial fusion via enhancing L-OPA1 protein expression. Mechanistically, TIM-4 regulated protein of L-OPA1 through the PI3K/AKT pathway, and TIM-4 interacted with ANXA2 to promote the activation of PI3K/AKT signaling. Collectively, TIM-4 promotes oxidative phosphorylation of lung cancer cells to accelerate tumor progress via ANXA2/PI3K/AKT/OPA1 axis, which sheds significant new lights on the potential role of TIM-4 in regulating tumor cell metabolism. |
| first_indexed | 2024-04-09T22:34:54Z |
| format | Article |
| id | doaj.art-57d55afae5c9412a8b67ef5af13b327e |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-09T22:34:54Z |
| publishDate | 2023-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-57d55afae5c9412a8b67ef5af13b327e2023-03-22T12:32:17ZengNature Publishing GroupCell Death and Disease2041-48892023-02-0114211310.1038/s41419-023-05678-3TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axisYuzhen Wang0Yingchun Wang1Wen Liu2Lu Ding3Xiaodi Zhang4Bo Wang5Zheng Tong6Xuetian Yue7Chunyang Li8Liyun Xu9Zhuanchang Wu10Xiaohong Liang11Chunhong Ma12Lifen Gao13Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityCell and Molecular Biology Laboratory, Zhoushan HospitalKey Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityAbstract Mitochondrial function and homeostasis are critical to the proliferation of lung cancer cells. T-cell immunoglobulin and mucin domain-containing molecule 4 (TIM-4) promotes the development and progression of lung cancer. However, the role of TIM-4 in mitochondria homeostasis in tumor cells remains completely unknown. In this study, we found that TIM-4 promoted growth and proliferation of lung cancer cells by the oxidative phosphorylation (OXPHOS) pathway. Consistently, inhibition of OXPHOS reversed TIM-4-induced proliferation of lung cancer cells. Notably, TIM-4 promoted mitochondrial fusion via enhancing L-OPA1 protein expression. Mechanistically, TIM-4 regulated protein of L-OPA1 through the PI3K/AKT pathway, and TIM-4 interacted with ANXA2 to promote the activation of PI3K/AKT signaling. Collectively, TIM-4 promotes oxidative phosphorylation of lung cancer cells to accelerate tumor progress via ANXA2/PI3K/AKT/OPA1 axis, which sheds significant new lights on the potential role of TIM-4 in regulating tumor cell metabolism.https://doi.org/10.1038/s41419-023-05678-3 |
| spellingShingle | Yuzhen Wang Yingchun Wang Wen Liu Lu Ding Xiaodi Zhang Bo Wang Zheng Tong Xuetian Yue Chunyang Li Liyun Xu Zhuanchang Wu Xiaohong Liang Chunhong Ma Lifen Gao TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis Cell Death and Disease |
| title | TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis |
| title_full | TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis |
| title_fullStr | TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis |
| title_full_unstemmed | TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis |
| title_short | TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis |
| title_sort | tim 4 orchestrates mitochondrial homeostasis to promote lung cancer progression via anxa2 pi3k akt opa1 axis |
| url | https://doi.org/10.1038/s41419-023-05678-3 |
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