Systematic Proteome and Lysine Succinylome Analysis Reveals the Enhanced Cell Migration by Hyposuccinylation in Esophageal Squamous Cell Cancer.

Systematic Proteome and Lysine Succinylome Analysis Reveals the Enhanced Cell Migration by Hyposuccinylation in Esophageal Squamous Cell Cancer. Mol Cell Proteomics. 2020 Oct 19;: Authors: Guo Z, Pan F, Peng L, Tian S, Jiao J, Liao L, Lu C, Zhai G, Wu Z, Dong H, Xu X, Wu J, Chen P, Bai X, Lin D, Xu LY, Li EM, Zhang K Abstract Esophageal squamous cell cancer (ESCC) is an aggressive malignancy with poor therapeutic outcomes. However, the alterations in proteins and post-translational modifications (PTMs) leading to the pathogenesis of ESCC remains unclear. Here, we provide the comprehensive characterization of the proteome, phosphorylome, lysine acetylome and succinylome for ESCC and matched control cells using quantitative proteomic approach. We identify abnormal protein and post-translational modification (PTM) pathways, including significantly downregulated lysine succinylation sites in cancer cells. Focusing on hyposuccinylation, we reveal that this altered PTM was enriched on enzymes of metabolic pathways inextricably linked with cancer metabolism. Importantly, ESCC malignant behaviors such as cell migration are inhibited once the level of succinylation was restored in vitro or in vivo This effect was further verified by mutations to disrupt succinylation sites in candidate proteins. Meanwhile, we found that succinylation has a negative regulatory effect on histone methylation to promote cancer migration. Finally, hyposuccinylatio...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Tags: Mol Cell Proteomics Source Type: research