Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma
Abstract Aberrant activation of Wnt/β-catenin signaling and dysregulation of metabolism have been frequently observed in lung cancer. However, the molecular mechanism by which Wnt/β-catenin signaling is regulated and the link between Wnt/β-catenin signaling and cancer metabolism are not fully unders...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04385-1 |
| _version_ | 1818833967113043968 |
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| author | Chenxi Zhong Ming Chen Yu Chen Feng Yao Wentao Fang |
| author_facet | Chenxi Zhong Ming Chen Yu Chen Feng Yao Wentao Fang |
| author_sort | Chenxi Zhong |
| collection | DOAJ |
| description | Abstract Aberrant activation of Wnt/β-catenin signaling and dysregulation of metabolism have been frequently observed in lung cancer. However, the molecular mechanism by which Wnt/β-catenin signaling is regulated and the link between Wnt/β-catenin signaling and cancer metabolism are not fully understood. In this study, we showed that the loss of dual serine/threonine tyrosine protein kinase (DSTYK) led to the activation of Wnt/β-catenin signaling and upregulation of its target gene, lactate dehydrogenase (LDHA), and thus the elevation of lactate. DSTYK phosphorylated the N-terminal domain of β-catenin and inhibited Wnt/β-catenin signaling, which led to the inhibition of cell growth, colony formation and tumorigenesis in a lung adenocarcinoma mouse model. DSTYK was downregulated in lung cancer tissues, and its expression was positively correlated with the survival of patients with lung adenocarcinoma. Taken together, these results demonstrate that the loss of DSTYK activates Wnt/β-catenin/LDHA signaling to promote the tumorigenesis of lung cancer and that DSTYK may be a therapeutic target. |
| first_indexed | 2024-12-19T02:27:20Z |
| format | Article |
| id | doaj.art-3fc6feca7773460b921414082930e6c8 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-19T02:27:20Z |
| publishDate | 2021-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-3fc6feca7773460b921414082930e6c82022-12-21T20:39:53ZengNature Publishing GroupCell Death and Disease2041-48892021-12-01121211010.1038/s41419-021-04385-1Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinomaChenxi Zhong0Ming Chen1Yu Chen2Feng Yao3Wentao Fang4Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong UniversityDepartment of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong UniversityDepartment of Thoracic Surgery, Shandong Zaozhuang Mining Group Central HospitalDepartment of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong UniversityDepartment of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong UniversityAbstract Aberrant activation of Wnt/β-catenin signaling and dysregulation of metabolism have been frequently observed in lung cancer. However, the molecular mechanism by which Wnt/β-catenin signaling is regulated and the link between Wnt/β-catenin signaling and cancer metabolism are not fully understood. In this study, we showed that the loss of dual serine/threonine tyrosine protein kinase (DSTYK) led to the activation of Wnt/β-catenin signaling and upregulation of its target gene, lactate dehydrogenase (LDHA), and thus the elevation of lactate. DSTYK phosphorylated the N-terminal domain of β-catenin and inhibited Wnt/β-catenin signaling, which led to the inhibition of cell growth, colony formation and tumorigenesis in a lung adenocarcinoma mouse model. DSTYK was downregulated in lung cancer tissues, and its expression was positively correlated with the survival of patients with lung adenocarcinoma. Taken together, these results demonstrate that the loss of DSTYK activates Wnt/β-catenin/LDHA signaling to promote the tumorigenesis of lung cancer and that DSTYK may be a therapeutic target.https://doi.org/10.1038/s41419-021-04385-1 |
| spellingShingle | Chenxi Zhong Ming Chen Yu Chen Feng Yao Wentao Fang Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma Cell Death and Disease |
| title | Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma |
| title_full | Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma |
| title_fullStr | Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma |
| title_full_unstemmed | Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma |
| title_short | Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma |
| title_sort | loss of dstyk activates wnt β catenin signaling and glycolysis in lung adenocarcinoma |
| url | https://doi.org/10.1038/s41419-021-04385-1 |
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