The potential of TAOK1 as a new therapeutic target for the treatment of cancer cachexia-associated muscle atrophy
Cancer cachexia, a multifactorial metabolic syndrome impacts 50–80 % cancer patients, is mainly characterized by skeletal muscle atrophy. In this study, we demonstrated that the thousand-and-one amino acid kinase 1 (TAOK1) was activated in both C2C12 myotubes treated with simulated cancer cachexia i...
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Elsevier
2025-06-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825001884 |
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| author | Ruiqin Zhang Nan Li Ke Yu Qiongsen Wang Meng Fan Xiongwen Zhang Xuan Liu |
| author_facet | Ruiqin Zhang Nan Li Ke Yu Qiongsen Wang Meng Fan Xiongwen Zhang Xuan Liu |
| author_sort | Ruiqin Zhang |
| collection | DOAJ |
| description | Cancer cachexia, a multifactorial metabolic syndrome impacts 50–80 % cancer patients, is mainly characterized by skeletal muscle atrophy. In this study, we demonstrated that the thousand-and-one amino acid kinase 1 (TAOK1) was activated in both C2C12 myotubes treated with simulated cancer cachexia injuries as well as in muscle tissues of mice inoculated with various types of tumor cells. Results of phosphoproteomic analysis also showed the increase in phosphorylation of TAOK1 in myotubes induced by simulated cancer cachexia injuries. Knockdown of TAOK1 in C2C12 myoblasts resulted in resistance to cancer cachexia-associated myotube atrophy. Comparing the protein expression profiles of C2C12-TAOK1-KO myotubes and that of control myotubes using proteomic analysis found that, TAOK1 knockout resulted in increased expression of muscle-related proteins and decreased expression of proteins related to MAPK pathway and ubiquitin-proteasome system (UPS). Results of Western blotting analysis confirmed the involvement of TAOK1/MAPK/FoxO3/UPS pathway in cancer cachexia-associated myotube atrophy, and suggested that TAOK1 knockout could ameliorate increased protein degradation but not decreased protein synthesis under cancer cachexia. CP43, a synthesized TAOK1 inhibitor, could ameliorate both in vitro myotube atrophy of C2C12 myotubes under simulated cancer cachexia injuries as well as in vivo muscle atrophy of cancer cachexia mice inoculating with C26 colon tumor cells. In conclusion, our study provides evidence that TAOK1 plays critical roles in activation of protein degradation under cancer cachexia thus targeting TAOK1 might be a potential therapy strategy for treatment of cancer cachexia-associated muscle atrophy. |
| format | Article |
| id | doaj-art-66ddafff0f624a17800b5a2b33d6b4b4 |
| institution | DOAJ |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-66ddafff0f624a17800b5a2b33d6b4b42025-08-20T03:07:17ZengElsevierPharmacological Research1096-11862025-06-0121610776310.1016/j.phrs.2025.107763The potential of TAOK1 as a new therapeutic target for the treatment of cancer cachexia-associated muscle atrophyRuiqin Zhang0Nan Li1Ke Yu2Qiongsen Wang3Meng Fan4Xiongwen Zhang5Xuan Liu6Shanghai Frontiers Science Center of TCM Chemical Biology; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaShanghai Frontiers Science Center of TCM Chemical Biology; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaShanghai Frontiers Science Center of TCM Chemical Biology; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaShanghai Frontiers Science Center of TCM Chemical Biology; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China; Corresponding authors.Shanghai Frontiers Science Center of TCM Chemical Biology; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding authors.Cancer cachexia, a multifactorial metabolic syndrome impacts 50–80 % cancer patients, is mainly characterized by skeletal muscle atrophy. In this study, we demonstrated that the thousand-and-one amino acid kinase 1 (TAOK1) was activated in both C2C12 myotubes treated with simulated cancer cachexia injuries as well as in muscle tissues of mice inoculated with various types of tumor cells. Results of phosphoproteomic analysis also showed the increase in phosphorylation of TAOK1 in myotubes induced by simulated cancer cachexia injuries. Knockdown of TAOK1 in C2C12 myoblasts resulted in resistance to cancer cachexia-associated myotube atrophy. Comparing the protein expression profiles of C2C12-TAOK1-KO myotubes and that of control myotubes using proteomic analysis found that, TAOK1 knockout resulted in increased expression of muscle-related proteins and decreased expression of proteins related to MAPK pathway and ubiquitin-proteasome system (UPS). Results of Western blotting analysis confirmed the involvement of TAOK1/MAPK/FoxO3/UPS pathway in cancer cachexia-associated myotube atrophy, and suggested that TAOK1 knockout could ameliorate increased protein degradation but not decreased protein synthesis under cancer cachexia. CP43, a synthesized TAOK1 inhibitor, could ameliorate both in vitro myotube atrophy of C2C12 myotubes under simulated cancer cachexia injuries as well as in vivo muscle atrophy of cancer cachexia mice inoculating with C26 colon tumor cells. In conclusion, our study provides evidence that TAOK1 plays critical roles in activation of protein degradation under cancer cachexia thus targeting TAOK1 might be a potential therapy strategy for treatment of cancer cachexia-associated muscle atrophy.http://www.sciencedirect.com/science/article/pii/S1043661825001884Cancer cachexiaMuscle atrophyTAOK1C2C12 myotubesTumor-bearing miceMAPK pathway |
| spellingShingle | Ruiqin Zhang Nan Li Ke Yu Qiongsen Wang Meng Fan Xiongwen Zhang Xuan Liu The potential of TAOK1 as a new therapeutic target for the treatment of cancer cachexia-associated muscle atrophy Pharmacological Research Cancer cachexia Muscle atrophy TAOK1 C2C12 myotubes Tumor-bearing mice MAPK pathway |
| title | The potential of TAOK1 as a new therapeutic target for the treatment of cancer cachexia-associated muscle atrophy |
| title_full | The potential of TAOK1 as a new therapeutic target for the treatment of cancer cachexia-associated muscle atrophy |
| title_fullStr | The potential of TAOK1 as a new therapeutic target for the treatment of cancer cachexia-associated muscle atrophy |
| title_full_unstemmed | The potential of TAOK1 as a new therapeutic target for the treatment of cancer cachexia-associated muscle atrophy |
| title_short | The potential of TAOK1 as a new therapeutic target for the treatment of cancer cachexia-associated muscle atrophy |
| title_sort | potential of taok1 as a new therapeutic target for the treatment of cancer cachexia associated muscle atrophy |
| topic | Cancer cachexia Muscle atrophy TAOK1 C2C12 myotubes Tumor-bearing mice MAPK pathway |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825001884 |
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