KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer
Abstract Glycolysis is the most predominant metabolic reprogramming of pancreatic cancer (PC), the underlying mechanism of which in PC cells remains unclear. In this study, we found for the first time that KIF15 promotes the glycolytic capacity of PC cells and PC tumor growth. Moreover, the expressi...
| 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/s41419-023-05679-2 |
| _version_ | 1797863431911505920 |
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| author | Gang Quan Jian Xu Jie Wang Xinyuan Liu Jichuan Xu Jianxin Jiang |
| author_facet | Gang Quan Jian Xu Jie Wang Xinyuan Liu Jichuan Xu Jianxin Jiang |
| author_sort | Gang Quan |
| collection | DOAJ |
| description | Abstract Glycolysis is the most predominant metabolic reprogramming of pancreatic cancer (PC), the underlying mechanism of which in PC cells remains unclear. In this study, we found for the first time that KIF15 promotes the glycolytic capacity of PC cells and PC tumor growth. Moreover, the expression of KIF15 was negatively correlated with the prognosis of PC patients. The ECAR and OCR measurements indicated that KIF15 knockdown significantly impaired the glycolytic capacity of PC cells. Western blotting demonstrated that the expression of glycolysis molecular markers decreased rapidly after the knockdown of KIF15. Further experiments revealed that KIF15 promoted the stability of PGK1 and its effect on PC cell glycolysis. Interestingly, the overexpression of KIF15 impaired the ubiquitination level of PGK1. To investigate the underlying mechanism by which KIF15 regulates the function of PGK1, we performed mass spectrometry (MS). The MS and Co-IP assay indicated that KIF15 recruited and enhanced the binding between PGK1 and USP10. The ubiquitination assay verified that KIF15 recruited and promoted the effect of USP10 on PGK1, thereby deubiquitinating PGK1. Through the construction of KIF15 truncators, we found that KIF15 is bound to PGK1 and USP10 through its coil2 domain. Together, our study demonstrated for the first time that KIF15 enhances the glycolytic capacity of PC through the recruitment of USP10 and PGK1, and that the KIF15/USP10/PGK1 axis may serve as an effective therapeutic agent for PC. |
| first_indexed | 2024-04-09T22:35:28Z |
| format | Article |
| id | doaj.art-e075e9bee955485f95d08850602a87f3 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-09T22:35:28Z |
| publishDate | 2023-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-e075e9bee955485f95d08850602a87f32023-03-22T12:32:28ZengNature Publishing GroupCell Death and Disease2041-48892023-02-0114211410.1038/s41419-023-05679-2KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancerGang Quan0Jian Xu1Jie Wang2Xinyuan Liu3Jichuan Xu4Jianxin Jiang5Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityAbstract Glycolysis is the most predominant metabolic reprogramming of pancreatic cancer (PC), the underlying mechanism of which in PC cells remains unclear. In this study, we found for the first time that KIF15 promotes the glycolytic capacity of PC cells and PC tumor growth. Moreover, the expression of KIF15 was negatively correlated with the prognosis of PC patients. The ECAR and OCR measurements indicated that KIF15 knockdown significantly impaired the glycolytic capacity of PC cells. Western blotting demonstrated that the expression of glycolysis molecular markers decreased rapidly after the knockdown of KIF15. Further experiments revealed that KIF15 promoted the stability of PGK1 and its effect on PC cell glycolysis. Interestingly, the overexpression of KIF15 impaired the ubiquitination level of PGK1. To investigate the underlying mechanism by which KIF15 regulates the function of PGK1, we performed mass spectrometry (MS). The MS and Co-IP assay indicated that KIF15 recruited and enhanced the binding between PGK1 and USP10. The ubiquitination assay verified that KIF15 recruited and promoted the effect of USP10 on PGK1, thereby deubiquitinating PGK1. Through the construction of KIF15 truncators, we found that KIF15 is bound to PGK1 and USP10 through its coil2 domain. Together, our study demonstrated for the first time that KIF15 enhances the glycolytic capacity of PC through the recruitment of USP10 and PGK1, and that the KIF15/USP10/PGK1 axis may serve as an effective therapeutic agent for PC.https://doi.org/10.1038/s41419-023-05679-2 |
| spellingShingle | Gang Quan Jian Xu Jie Wang Xinyuan Liu Jichuan Xu Jianxin Jiang KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer Cell Death and Disease |
| title | KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer |
| title_full | KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer |
| title_fullStr | KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer |
| title_full_unstemmed | KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer |
| title_short | KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer |
| title_sort | kif15 is essential for usp10 mediated pgk1 deubiquitination during the glycolysis of pancreatic cancer |
| url | https://doi.org/10.1038/s41419-023-05679-2 |
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