KCNJ15 deficiency promotes drug resistance via affecting the function of lysosomes
The altered lysosomal function can induce drug redistribution which leads to drug resistance and poor prognosis for cancer patients. V-ATPase, an ATP-driven proton pump positioned at lysosomal surfaces, is responsible for maintaining the stability of lysosome. Herein, we reported that the potassium...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Asian Journal of Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1818087623000417 |
| _version_ | 1827915250682298368 |
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| author | Xinbo Qiao Yixiao Zhang Zhan Zhang Nan Niu Haonan Li Lisha Sun Qingtian Ma Jiawen Bu Jinchi Liu Guanglei Chen Jinqi Xue Yongliang Yang Caigang Liu |
| author_facet | Xinbo Qiao Yixiao Zhang Zhan Zhang Nan Niu Haonan Li Lisha Sun Qingtian Ma Jiawen Bu Jinchi Liu Guanglei Chen Jinqi Xue Yongliang Yang Caigang Liu |
| author_sort | Xinbo Qiao |
| collection | DOAJ |
| description | The altered lysosomal function can induce drug redistribution which leads to drug resistance and poor prognosis for cancer patients. V-ATPase, an ATP-driven proton pump positioned at lysosomal surfaces, is responsible for maintaining the stability of lysosome. Herein, we reported that the potassium voltage-gated channel subfamily J member 15 (KCNJ15) protein, which may bind to V-ATPase, can regulate the function of lysosome. The deficiency of KCNJ15 protein in breast cancer cells led to drug aggregation as well as reduction of drug efficacy. The application of the V-ATPase inhibitor could inhibit the binding between KCNJ15 and V-ATPase, contributing to the amelioration of drug resistance. Clinical data analysis revealed that KCNJ15 deficiency was associated with higher histological grading, advanced stages, more metastases of lymph nodes, and shorter disease free survival of patients with breast cancer. KCNJ15 expression level is positively correlated with a high response rate after receiving neoadjuvant chemotherapy. Moreover, we revealed that the small molecule drug CMA/BAF can reverse drug resistance by disrupting the interaction between KCNJ15 and lysosomes. In conclusion, KCNJ15 could be identified as an underlying indicator for drug resistance and survival of breast cancer, which might guide the choice of therapeutic strategies. |
| first_indexed | 2024-03-13T02:56:49Z |
| format | Article |
| id | doaj.art-b25602f28e464d2ba28c01e6b6e459c0 |
| institution | Directory Open Access Journal |
| issn | 1818-0876 |
| language | English |
| last_indexed | 2024-03-13T02:56:49Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Asian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-b25602f28e464d2ba28c01e6b6e459c02023-06-28T04:29:21ZengElsevierAsian Journal of Pharmaceutical Sciences1818-08762023-05-01183100814KCNJ15 deficiency promotes drug resistance via affecting the function of lysosomesXinbo Qiao0Yixiao Zhang1Zhan Zhang2Nan Niu3Haonan Li4Lisha Sun5Qingtian Ma6Jiawen Bu7Jinchi Liu8Guanglei Chen9Jinqi Xue10Yongliang Yang11Caigang Liu12Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang 110000, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang 110000, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang 110000, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang 110000, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang 110000, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang 110000, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang 110000, ChinaSchool of Bioengineering, Dalian University of Technology, Dalian 116000, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang 110000, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang 110000, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang 110000, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang 110000, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang 110000, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang 110000, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang 110000, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang 110000, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang 110000, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang 110000, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; School of Bioengineering, Dalian University of Technology, Dalian 116000, China; Corresponding authors.Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110000, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang 110000, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang 110000, China; Corresponding authors.The altered lysosomal function can induce drug redistribution which leads to drug resistance and poor prognosis for cancer patients. V-ATPase, an ATP-driven proton pump positioned at lysosomal surfaces, is responsible for maintaining the stability of lysosome. Herein, we reported that the potassium voltage-gated channel subfamily J member 15 (KCNJ15) protein, which may bind to V-ATPase, can regulate the function of lysosome. The deficiency of KCNJ15 protein in breast cancer cells led to drug aggregation as well as reduction of drug efficacy. The application of the V-ATPase inhibitor could inhibit the binding between KCNJ15 and V-ATPase, contributing to the amelioration of drug resistance. Clinical data analysis revealed that KCNJ15 deficiency was associated with higher histological grading, advanced stages, more metastases of lymph nodes, and shorter disease free survival of patients with breast cancer. KCNJ15 expression level is positively correlated with a high response rate after receiving neoadjuvant chemotherapy. Moreover, we revealed that the small molecule drug CMA/BAF can reverse drug resistance by disrupting the interaction between KCNJ15 and lysosomes. In conclusion, KCNJ15 could be identified as an underlying indicator for drug resistance and survival of breast cancer, which might guide the choice of therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S1818087623000417Breast cancerCancer progressionDrug resistanceLysosomeKCNJ15 |
| spellingShingle | Xinbo Qiao Yixiao Zhang Zhan Zhang Nan Niu Haonan Li Lisha Sun Qingtian Ma Jiawen Bu Jinchi Liu Guanglei Chen Jinqi Xue Yongliang Yang Caigang Liu KCNJ15 deficiency promotes drug resistance via affecting the function of lysosomes Asian Journal of Pharmaceutical Sciences Breast cancer Cancer progression Drug resistance Lysosome KCNJ15 |
| title | KCNJ15 deficiency promotes drug resistance via affecting the function of lysosomes |
| title_full | KCNJ15 deficiency promotes drug resistance via affecting the function of lysosomes |
| title_fullStr | KCNJ15 deficiency promotes drug resistance via affecting the function of lysosomes |
| title_full_unstemmed | KCNJ15 deficiency promotes drug resistance via affecting the function of lysosomes |
| title_short | KCNJ15 deficiency promotes drug resistance via affecting the function of lysosomes |
| title_sort | kcnj15 deficiency promotes drug resistance via affecting the function of lysosomes |
| topic | Breast cancer Cancer progression Drug resistance Lysosome KCNJ15 |
| url | http://www.sciencedirect.com/science/article/pii/S1818087623000417 |
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