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CSNK2A1-mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer
1Translational Medicine Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 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.
Insights
High mobility group AT-hook 2 (HMGA2) promotes chemoresistance in cervical cancer by interacting with casein kinase II A1 (CSNK2A1). Inhibiting CSNK2A1 may overcome cisplatin resistance, improving cancer treatment efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Chemoresistance limits anti-cancer drug effectiveness, particularly in cervical cancer prevalent in developing nations.
- High mobility group AT-hook 2 (HMGA2) is an oncogenic protein implicated in tumor development, but its role in cervical cancer chemoresistance is unknown.
Purpose of the Study:
- To investigate the role of HMGA2 in cisplatin resistance in cervical cancer.
- To explore the interaction between HMGA2 and casein kinase II A1 (CSNK2A1) in this context.
Main Methods:
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify protein interactions.
- Immunofluorescence to confirm co-localization of HMGA2 and CSNK2A1.
- Immunoprecipitation assays to detect protein binding.
- Treatment with CX-4945, a CSNK2A1 inhibitor.
Main Results:
- HMGA2 is highly expressed in cervical cancer and inversely correlated with cisplatin-induced cell death.
- HMGA2 interacts with and co-localizes with CSNK2A1 in the nucleus.
- Cisplatin treatment enhances the interaction between CSNK2A1 and HMGA2, leading to HMGA2 phosphorylation.
- CSNK2A1 inhibition by CX-4945 reduces HMGA2 phosphorylation and sensitizes cells to cisplatin.
Conclusions:
- CSNK2A1-dependent phosphorylation of HMGA2 contributes to cisplatin resistance in cervical cancer.
- HMGA2 phosphorylation presents a potential predictive biomarker and therapeutic target for enhancing chemotherapeutic efficacy.
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