Cargando…
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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409285/ https://www.ncbi.nlm.nih.gov/pubmed/34375503 http://dx.doi.org/10.1002/2211-5463.13270 |
_version_ | 1783746967534305280 |
---|---|
author | Fan, Haonan Ou, Qifeng Su, Qiao Li, Guanman Deng, Zhijuan Huang, Xiaohui Bi, Jiong |
author_facet | Fan, Haonan Ou, Qifeng Su, Qiao Li, Guanman Deng, Zhijuan Huang, Xiaohui Bi, Jiong |
author_sort | Fan, Haonan |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8409285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84092852021-09-03 ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells Fan, Haonan Ou, Qifeng Su, Qiao Li, Guanman Deng, Zhijuan Huang, Xiaohui Bi, Jiong FEBS Open Bio Research Articles 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. John Wiley and Sons Inc. 2021-08-22 /pmc/articles/PMC8409285/ /pubmed/34375503 http://dx.doi.org/10.1002/2211-5463.13270 Text en © 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Fan, Haonan Ou, Qifeng Su, Qiao Li, Guanman Deng, Zhijuan Huang, Xiaohui Bi, Jiong ZIPK activates the IL‐6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells |
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 | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409285/ https://www.ncbi.nlm.nih.gov/pubmed/34375503 http://dx.doi.org/10.1002/2211-5463.13270 |
work_keys_str_mv | AT fanhaonan zipkactivatestheil6stat3signalingpathwayandpromotescisplatinresistanceingastriccancercells AT ouqifeng zipkactivatestheil6stat3signalingpathwayandpromotescisplatinresistanceingastriccancercells AT suqiao zipkactivatestheil6stat3signalingpathwayandpromotescisplatinresistanceingastriccancercells AT liguanman zipkactivatestheil6stat3signalingpathwayandpromotescisplatinresistanceingastriccancercells AT dengzhijuan zipkactivatestheil6stat3signalingpathwayandpromotescisplatinresistanceingastriccancercells AT huangxiaohui zipkactivatestheil6stat3signalingpathwayandpromotescisplatinresistanceingastriccancercells AT bijiong zipkactivatestheil6stat3signalingpathwayandpromotescisplatinresistanceingastriccancercells |