Comprehensive proteomics analysis reveals novel Nek2-regulated pathways and therapeutic targets in cancer

Abstract

The mitotic kinase Nek2, often overexpressed in various cancers, plays a pivotal role in key cellular processes like the cell cycle, proliferation, and drug resistance. As a result, targeting Nek2 has become an appealing strategy for cancer therapy. To gain a comprehensive understanding of the cellular changes associated with Nek2 activity modulation, we performed a global proteomics analysis using LC-MS/MS. Through bioinformatics tools, we identified molecular pathways that are differentially regulated in cancer cells with Nek2 overexpression or depletion. Of the 1815 proteins identified, 358 exceeded the 20 % significance threshold. By integrating LC-MS/MS data with cancer patient datasets, we observed a strong correlation between Nek2 expression and the levels of KIF20B and RRM1. Silencing Nek2 led to a significant reduction in KIF20B and RRM1 protein levels, and potential phosphorylation sites for these proteins by Nek2 were identified. In summary, our data suggests that KIF20B and RRM1 are promising therapeutic targets, either independently or alongside Nek2 inhibitors, to improve clinical outcomes. Further analyses are necessary to fully understand Nek2's interactions with these proteins and their clinical relevance.