1. Academic Validation
  2. CSNK2A1-mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer

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

  • FEBS Open Bio. 2021 Jun 11;11(8):2245-2255. doi: 10.1002/2211-5463.13228.
Zhan Shi 1 Ding Wu 2 Hao Xu 3 Ju Yang 4 Xiaoqing Sun 5
Affiliations

Affiliations

  • 1 Translational Medicine Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Department of Urology, Jinling Hospital, Nanjing Medical University, Nanjing, China.
  • 3 Department of Urology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China.
  • 4 The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China.
  • 5 Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Abstract

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.

Keywords

CSNK2A1; HMGA2; cervical cancer; chemoresistance; cisplatin.

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