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

Z Shi, D Wu, H Xu, J Yang, X Sun - FEBS Open bio, 2021 - Wiley Online Library
Z Shi, D Wu, H Xu, J Yang, X Sun
FEBS Open bio, 2021Wiley Online Library
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 …
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.
Wiley Online Library