CtBP modulates Snail-mediated tumor invasion in Drosophila
Abstract Cancer is one of the most fatal diseases that threaten human health, whereas more than 90% mortality of cancer patients is caused by tumor metastasis, rather than the growth of primary tumors. Thus, how to effectively control or even reverse the migration of tumor cells is of great signific...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-08-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-021-00516-x |
| _version_ | 1818694281902161920 |
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| author | Chenxi Wu Xiang Ding Zhuojie Li Yuanyuan Huang Qian Xu Rui Zou Mingyang Zhao Hong Chang Chunhua Jiang Xiaojin La Gufa Lin Wenzhe Li Lei Xue |
| author_facet | Chenxi Wu Xiang Ding Zhuojie Li Yuanyuan Huang Qian Xu Rui Zou Mingyang Zhao Hong Chang Chunhua Jiang Xiaojin La Gufa Lin Wenzhe Li Lei Xue |
| author_sort | Chenxi Wu |
| collection | DOAJ |
| description | Abstract Cancer is one of the most fatal diseases that threaten human health, whereas more than 90% mortality of cancer patients is caused by tumor metastasis, rather than the growth of primary tumors. Thus, how to effectively control or even reverse the migration of tumor cells is of great significance for cancer therapy. CtBP, a transcriptional cofactor displaying high expression in a variety of human cancers, has become one of the main targets for cancer prediction, diagnosis, and treatment. The roles of CtBP in promoting tumorigenesis have been well studied in vitro, mostly based on gain-of-function, while its physiological functions in tumor invasion and the underlying mechanism remain largely elusive. Snail (Sna) is a well-known transcription factor involved in epithelial-to-mesenchymal transition (EMT) and tumor invasion, yet the mechanism that regulates Sna activity has not been fully understood. Using Drosophila as a model organism, we found that depletion of CtBP or snail (sna) suppressed RasV12/lgl -/- -triggered tumor growth and invasion, and disrupted cell polarity-induced invasive cell migration. In addition, loss of CtBP inhibits RasV12/Sna-induced tumor invasion and Sna-mediated invasive cell migration. Furthermore, both CtBP and Sna are physiologically required for developmental cell migration during thorax closure. Finally, Sna activates the JNK signaling and promotes JNK-dependent cell invasion. Given that CtBP physically interacts with Sna, our data suggest that CtBP and Sna may form a transcriptional complex that regulates JNK-dependent tumor invasion and cell migration in vivo. |
| first_indexed | 2024-12-17T13:27:06Z |
| format | Article |
| id | doaj.art-a46c3d55d16a431391c9b94bb6e85ca7 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-12-17T13:27:06Z |
| publishDate | 2021-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-a46c3d55d16a431391c9b94bb6e85ca72022-12-21T21:46:42ZengNature Publishing GroupCell Death Discovery2058-77162021-08-017111310.1038/s41420-021-00516-xCtBP modulates Snail-mediated tumor invasion in DrosophilaChenxi Wu0Xiang Ding1Zhuojie Li2Yuanyuan Huang3Qian Xu4Rui Zou5Mingyang Zhao6Hong Chang7Chunhua Jiang8Xiaojin La9Gufa Lin10Wenzhe Li11Lei Xue12The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji UniversityThe First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji UniversityThe First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji UniversityThe First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji UniversityCollege of Integrative Medicine, Fujian University of Traditional Chinese MedicineThe First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji UniversityThe First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji UniversityCollege of Traditional Chinese Medicine, North China University of Science and TechnologyCollege of Traditional Chinese Medicine, North China University of Science and TechnologyCollege of Traditional Chinese Medicine, North China University of Science and TechnologyKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityThe First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji UniversityThe First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji UniversityAbstract Cancer is one of the most fatal diseases that threaten human health, whereas more than 90% mortality of cancer patients is caused by tumor metastasis, rather than the growth of primary tumors. Thus, how to effectively control or even reverse the migration of tumor cells is of great significance for cancer therapy. CtBP, a transcriptional cofactor displaying high expression in a variety of human cancers, has become one of the main targets for cancer prediction, diagnosis, and treatment. The roles of CtBP in promoting tumorigenesis have been well studied in vitro, mostly based on gain-of-function, while its physiological functions in tumor invasion and the underlying mechanism remain largely elusive. Snail (Sna) is a well-known transcription factor involved in epithelial-to-mesenchymal transition (EMT) and tumor invasion, yet the mechanism that regulates Sna activity has not been fully understood. Using Drosophila as a model organism, we found that depletion of CtBP or snail (sna) suppressed RasV12/lgl -/- -triggered tumor growth and invasion, and disrupted cell polarity-induced invasive cell migration. In addition, loss of CtBP inhibits RasV12/Sna-induced tumor invasion and Sna-mediated invasive cell migration. Furthermore, both CtBP and Sna are physiologically required for developmental cell migration during thorax closure. Finally, Sna activates the JNK signaling and promotes JNK-dependent cell invasion. Given that CtBP physically interacts with Sna, our data suggest that CtBP and Sna may form a transcriptional complex that regulates JNK-dependent tumor invasion and cell migration in vivo.https://doi.org/10.1038/s41420-021-00516-x |
| spellingShingle | Chenxi Wu Xiang Ding Zhuojie Li Yuanyuan Huang Qian Xu Rui Zou Mingyang Zhao Hong Chang Chunhua Jiang Xiaojin La Gufa Lin Wenzhe Li Lei Xue CtBP modulates Snail-mediated tumor invasion in Drosophila Cell Death Discovery |
| title | CtBP modulates Snail-mediated tumor invasion in Drosophila |
| title_full | CtBP modulates Snail-mediated tumor invasion in Drosophila |
| title_fullStr | CtBP modulates Snail-mediated tumor invasion in Drosophila |
| title_full_unstemmed | CtBP modulates Snail-mediated tumor invasion in Drosophila |
| title_short | CtBP modulates Snail-mediated tumor invasion in Drosophila |
| title_sort | ctbp modulates snail mediated tumor invasion in drosophila |
| url | https://doi.org/10.1038/s41420-021-00516-x |
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