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  • SRPK1 acetylation modulates alternative splicing to regulate cisplatin resistance in breast cancer cells.

SRPK1 acetylation modulates alternative splicing to regulate cisplatin resistance in breast cancer cells.

Communications biology (2020-05-29)
Cheng Wang, Zhihong Zhou, Charannya Sozheesvari Subhramanyam, Qiong Cao, Zealyn Shi Lin Heng, Wen Liu, Xiangdong Fu, Qidong Hu
ABSTRACT

Cisplatin and other platinum-based compounds are frequently used to treat breast cancer, but their utility is severely compromised by drug resistance. Many genes dictating drug responsiveness are subject to pre-mRNA alternative splicing which is regulated by key kinases such as the serine-arginine protein kinase 1 (SRPK1). However, its contribution to drug resistance remains controversial. In this study, we have identified that Tip60-mediated acetylation of SRPK1 is closely associated with chemotherapy sensitivity. In breast cancer cells, cisplatin induced SRPK1 acetylation but in the corresponding resistant cells, it reduced acetylation yet increased phosphorylation and kinase activity of SRPK1, favouring the splicing of some anti-apoptotic variants. Significantly, the cisplatin-resistant cells could be re-sensitized by enhancing SRPK1 acetylation or inhibiting its kinase activity. Hence, our study reveals a key role of SRPK1 in the development of cisplatin resistance in breast cancer cells and suggests a potential therapeutic avenue for overcoming chemotherapy resistance.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
SRPIN340, ≥98% (HPLC)
Sigma-Aldrich
Anti-TIP60 Rabbit pAb, liquid, Calbiochem®