ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells
Gastric cancer is one of the most common malignant cancers globally. Chemotherapy resistance remains a major obstacle in the treatment of gastric cancer, and the molecular mechanisms underlying drug resistance are still not well understood. We previously reported that Zipper interacting protein kina...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-09-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.13270 |
| _version_ | 1818574645558771712 |
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| author | Haonan Fan Qifeng Ou Qiao Su Guanman Li Zhijuan Deng Xiaohui Huang Jiong Bi |
| author_facet | Haonan Fan Qifeng Ou Qiao Su Guanman Li Zhijuan Deng Xiaohui Huang Jiong Bi |
| author_sort | Haonan Fan |
| collection | DOAJ |
| description | Gastric cancer is one of the most common malignant cancers globally. Chemotherapy resistance remains a major obstacle in the treatment of gastric cancer, and the molecular mechanisms underlying drug resistance are still not well understood. We previously reported that Zipper interacting protein kinase (ZIPK), also known as death‐associated protein kinase3, exerts an oncogenic effect on gastric cancer via activation of Akt/NF‐κB signaling and promotion of stemness. Here, we explored the roles of ZIPK in cisplatin resistance. We report that ZIPK enhances cell proliferation and invasion and reduces the antitumor activity of cisplatin in gastric cancer. In addition, our western blot data suggest that ZIPK activated the IL‐6/STAT3 signaling pathway. Furthermore, ZIPK increased the expression of IL‐6 and multidrug‐resistance genes. Using the STAT3 inhibitor stattic to block the IL‐6/STAT3 signaling pathway strongly increased the sensitivity of ZIPK‐expressed cells to cisplatin. In conclusion, ZIPK may play a role in cisplatin resistance through activation of the IL‐6/ STAT3 signaling pathway. Inhibition of STAT3 in gastric cancer overexpressing ZIPK might have potential to improve the efficacy of cisplatin. |
| first_indexed | 2024-12-15T00:29:18Z |
| format | Article |
| id | doaj.art-1d63c9ddcab347cd953ce67dd929a2bf |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-12-15T00:29:18Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-1d63c9ddcab347cd953ce67dd929a2bf2022-12-21T22:42:04ZengWileyFEBS Open Bio2211-54632021-09-011192655266710.1002/2211-5463.13270ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cellsHaonan Fan0Qifeng Ou1Qiao Su2Guanman Li3Zhijuan Deng4Xiaohui Huang5Jiong Bi6Laboratory of General Surgery The First Affiliated Hospital Sun Yat‐sen University Guangzhou ChinaLaboratory of General Surgery The First Affiliated Hospital Sun Yat‐sen University Guangzhou ChinaLaboratory Animal Center The First Affiliated Hospital Sun Yat‐sen University Guangzhou ChinaLaboratory of General Surgery The First Affiliated Hospital Sun Yat‐sen University Guangzhou ChinaLaboratory of General Surgery The First Affiliated Hospital Sun Yat‐sen University Guangzhou ChinaLaboratory of General Surgery The First Affiliated Hospital Sun Yat‐sen University Guangzhou ChinaLaboratory of General Surgery The First Affiliated Hospital Sun Yat‐sen University Guangzhou ChinaGastric cancer is one of the most common malignant cancers globally. Chemotherapy resistance remains a major obstacle in the treatment of gastric cancer, and the molecular mechanisms underlying drug resistance are still not well understood. We previously reported that Zipper interacting protein kinase (ZIPK), also known as death‐associated protein kinase3, exerts an oncogenic effect on gastric cancer via activation of Akt/NF‐κB signaling and promotion of stemness. Here, we explored the roles of ZIPK in cisplatin resistance. We report that ZIPK enhances cell proliferation and invasion and reduces the antitumor activity of cisplatin in gastric cancer. In addition, our western blot data suggest that ZIPK activated the IL‐6/STAT3 signaling pathway. Furthermore, ZIPK increased the expression of IL‐6 and multidrug‐resistance genes. Using the STAT3 inhibitor stattic to block the IL‐6/STAT3 signaling pathway strongly increased the sensitivity of ZIPK‐expressed cells to cisplatin. In conclusion, ZIPK may play a role in cisplatin resistance through activation of the IL‐6/ STAT3 signaling pathway. Inhibition of STAT3 in gastric cancer overexpressing ZIPK might have potential to improve the efficacy of cisplatin.https://doi.org/10.1002/2211-5463.13270chemotherapy resistancegastric cancerzipper interacting protein kinaseIL‐6/STAT3 signaling pathway |
| spellingShingle | Haonan Fan Qifeng Ou Qiao Su Guanman Li Zhijuan Deng Xiaohui Huang Jiong Bi ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells FEBS Open Bio chemotherapy resistance gastric cancer zipper interacting protein kinase IL‐6/STAT3 signaling pathway |
| title | ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells |
| title_full | ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells |
| title_fullStr | ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells |
| title_full_unstemmed | ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells |
| title_short | ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells |
| title_sort | zipk activates the il 6 stat3 signaling pathway and promotes cisplatin resistance in gastric cancer cells |
| topic | chemotherapy resistance gastric cancer zipper interacting protein kinase IL‐6/STAT3 signaling pathway |
| url | https://doi.org/10.1002/2211-5463.13270 |
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