CSNK2A1‐mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer. Issue 8 (12th July 2021)

• Record Type: Journal Article
• Authors: Shi, Zhan; Wu, Ding; Xu, Hao; Yang, Ju; Sun, Xiaoqing
• Is Part Of: FEBS open bio. Volume 11:Issue 8(2021)
• Page Start: 2245
• Page End: 2255
• Publication Date: 2021-07-12
• Subjects: cervical cancer -- chemoresistance -- cisplatin -- CSNK2A1 -- HMGA2; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.13228
• Languages: English
• ISSNs: 2211-5463

Abstract

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. Abstract : The oncogenic protein high mobility group AT‐hook 2 (HMGA2) participates in the development and progression of tumors. Cisplatin may enhance the interaction between HMGA2 and serine‐threonine kinase casein kinase II A1, thereby causing enhancement of HMGA2 phosphorylation in a time‐ and dose‐dependent manner, which in turn affects the bcl‐2/bax pathway and the resistance of cervical cancer cells to cisplatin.