Roles of eEF-2 kinase in cancer

Objective To provide a summary of the relationship between the eEF-2/eEF-2 kinase pathway and each phase of malignant neoplasms. The specific importance of this relationship in understanding and treating cancer was also explored. Data sources The data used in this review were mainly obtained from the articles listed in HighWire and PubMed in English. The search terms were ＂eEF-2 kinase＂, ＂oncogenesis＂, and ＂tumor progression＂. Study selection This review relates the observation that the overexpression of eEF-2 kinase is seen in cancer, and highlights that it has emerged as promoting the development of many malignant phenotypes when unregulated. This includes increasing the replicative potential of cells, angiogenesis, invasion and metastasis, and evasion of apoptosis. Results eEF-2 kinase is a structurally and functionally unique protein kinase. The increased activity of this protein in cancer cells is a protective mechanism to allow tumor growth and evolution, and resist cell death through the eEF-2/eEF-2 kinase pathway, but it also makes a potential target for therapy. Conclusion eEF-2 kinase fills critical niches in the life of a cancer cell and the eEF-2/eEF-2 kinase pathway is a key biochemical sensor.

Integrative proteomics reveals the role of E3 ubiquitin ligase SYVN1 in hepatocellular carcinoma metastasis

Background:Tumor metastasis is a major factor for poor prognosis of hepatocellular carcinoma(HCC),but the relationship between ubiquitination and metastasis need to be studiedmore systematically.We analyzed the ubiquitinome of HCC in this study to have a more comprehensive insight into human HCC metastasis.Methods:The protein ubiquitination levels in 15 HCC specimens with vascular invasion and 15 without vascular invasion were detected by ubiquitinome.Proteins with significantly different ubiquitination levels between HCCs with and without vascular invasion were used to predict E3 ubiquitin ligases associated with tumor metastasis.The topological network of protein substrates and corresponding E3 ubiquitin ligaseswas constructed to identify the key E3 ubiquitin ligase.Besides,the growth,migration and invasion ability of LM3 and HUH7 hepatoma cell lines with andwithout SYVN1 expression interferencewere measured by cell proliferation assay,subcutaneous tumor assay,umphal vein endothelium tube formation assay,transwell migration and invasion assays.Finally,the interacting proteins of SYVN1 were screened and verified by protein interaction omics,immunofluorescence,and immunoprecipitation.Ubiquitin levels of related protein substrates in LM3 and HUH7 cells were compared in negative control,SYVN1 knockdown,and SYVN1 overexpression groups.Results:In this study,our whole-cell proteomic dataset and ubiquitinomic dataset contained approximately 5600 proteins and 12,000 ubiquitinated sites.We discovered increased ubiquitinated sites with shorter ubiquitin chains during the progression ofHCC metastasis.In addition,proteomic and ubiquitinomic analyses revealed that high expression of E3 ubiquitin-protein ligase SYVN1 is related with tumor metastasis.Furthermore,we found that SYVN1 interacted with heat shock protein 90(HSP90)and impacted the ubiquitination of eukaryotic elongation factor 2 kinase(EEF2K).Conclusions:The ubiquitination profiles of HCC with and without vascular invasion were significantly different.SYVN1 was the most important E3 ubiquitin-protein ligase responsible for this phenomenon,and itwas related with tumormetastasis and growth.Therefore,SYVN1might be a potential therapeutic target for HCC.