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CSNK2A1‐mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer

The development of chemoresistance reduces the efficacy of anti‐cancer drugs. Cervical cancer is still one of the most common cancer types in developing countries. The oncogenic protein high mobility group AT‐hook 2 (HMGA2) is involved in the development and progression of tumors, although its role...

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Autores principales: Shi, Zhan, Wu, Ding, Xu, Hao, Yang, Ju, Sun, Xiaoqing
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/PMC8329774/
https://www.ncbi.nlm.nih.gov/pubmed/34115920
http://dx.doi.org/10.1002/2211-5463.13228
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author Shi, Zhan
Wu, Ding
Xu, Hao
Yang, Ju
Sun, Xiaoqing
author_facet Shi, Zhan
Wu, Ding
Xu, Hao
Yang, Ju
Sun, Xiaoqing
author_sort Shi, Zhan
collection PubMed
description The development of chemoresistance reduces the efficacy of anti‐cancer drugs. Cervical cancer is still one of the most common cancer types in developing countries. The oncogenic protein high mobility group AT‐hook 2 (HMGA2) is involved in the development and progression of tumors, although its role in chemoresistance of cervical cancer remains unclear. Here, we report that HMGA2 is highly expressed in cervical cancer and negatively correlated with cisplatin‐induced cell death. We performed liquid chromatography‐tandem mass spectrometry to demonstrate that HMGA2 has high potential to interact with casein kinase II A1 (CSNK2A1). Moreover, we observed that HMGA2 co‐localizes with CSNK2A1 in the nucleus by immunofluorescence. Binding of HMGA2‐CSNK2A1 was detected by immunoprecipitation assays. In addition, we identified that cisplatin induces an interaction between CSNK2A1 and HMGA2, thereby promoting the phosphorylation of HMGA2. CX‐4945, a CSNK2A1 inhibitor, could inhibit the phosphorylation of HMGA2 and sensitize tumor cells to cisplatin. Our results reveal that CSNK2A1‐dependent HMGA2 phosphorylation may partially underlie cisplatin‐resistance in cervical cancer, suggesting that HMGA2 phosphorylation may have potential as a predicative biomarker and therapeutic target to improve chemotherapeutic efficacy.
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spelling pubmed-83297742021-08-09 CSNK2A1‐mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer Shi, Zhan Wu, Ding Xu, Hao Yang, Ju Sun, Xiaoqing FEBS Open Bio Research Articles The development of chemoresistance reduces the efficacy of anti‐cancer drugs. Cervical cancer is still one of the most common cancer types in developing countries. The oncogenic protein high mobility group AT‐hook 2 (HMGA2) is involved in the development and progression of tumors, although its role in chemoresistance of cervical cancer remains unclear. Here, we report that HMGA2 is highly expressed in cervical cancer and negatively correlated with cisplatin‐induced cell death. We performed liquid chromatography‐tandem mass spectrometry to demonstrate that HMGA2 has high potential to interact with casein kinase II A1 (CSNK2A1). Moreover, we observed that HMGA2 co‐localizes with CSNK2A1 in the nucleus by immunofluorescence. Binding of HMGA2‐CSNK2A1 was detected by immunoprecipitation assays. In addition, we identified that cisplatin induces an interaction between CSNK2A1 and HMGA2, thereby promoting the phosphorylation of HMGA2. CX‐4945, a CSNK2A1 inhibitor, could inhibit the phosphorylation of HMGA2 and sensitize tumor cells to cisplatin. Our results reveal that CSNK2A1‐dependent HMGA2 phosphorylation may partially underlie cisplatin‐resistance in cervical cancer, suggesting that HMGA2 phosphorylation may have potential as a predicative biomarker and therapeutic target to improve chemotherapeutic efficacy. John Wiley and Sons Inc. 2021-07-12 /pmc/articles/PMC8329774/ /pubmed/34115920 http://dx.doi.org/10.1002/2211-5463.13228 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
Shi, Zhan
Wu, Ding
Xu, Hao
Yang, Ju
Sun, Xiaoqing
CSNK2A1‐mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer
title CSNK2A1‐mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer
title_full CSNK2A1‐mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer
title_fullStr CSNK2A1‐mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer
title_full_unstemmed CSNK2A1‐mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer
title_short CSNK2A1‐mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer
title_sort csnk2a1‐mediated phosphorylation of hmga2 modulates cisplatin resistance in cervical cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329774/
https://www.ncbi.nlm.nih.gov/pubmed/34115920
http://dx.doi.org/10.1002/2211-5463.13228
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