Integrated proteomic and phosphoproteomic analyses of cisplatin-sensitive and resistant bladder cancer cells reveal CDK2 network as a key therapeutic target.

Cancer Letters
Jae Hun JungJayoung Kim

Abstract

Cisplatin-based chemotherapy is currently part of the standard of care for bladder cancer (BC). Unfortunately, some patients respond poorly to chemotherapy and have acquired or developed resistance. The molecular mechanisms underlying this resistance remain unclear. Here, we introduce a multidimensional proteomic analysis of a cisplatin-resistant BC model that provides different levels of protein information, including that of the global proteome and phosphoproteome. To characterize the global proteome and phosphoproteome in cisplatin-resistant BC cells, liquid chromatography-mass spectrometry/mass spectrometry experiments combined with comprehensive bioinformatics analysis were performed. Perturbed expression and phosphorylation levels of key kinases associated with cisplatin resistance were further studied using various cell biology assays, including western blot analysis. Analyses of protein expression and phosphorylation identified significantly altered proteins, which were also EGF-dependent and independent. This suggests that protein phosphorylation plays a significant role in cisplatin-resistant BC. Additional network analysis of significantly altered proteins revealed CDK2, CHEK1, and ERBB2 as central regulators mediati...Continue Reading

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Mar 31, 2019·Expert Review of Proteomics·Yao AnCanhua Huang
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Feb 10, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shuailong JiaZhifeng Du
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Jun 8, 2021·Molecular Therapy Oncolytics·Xiao-Li YangDa Fu

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