Cancer Cell：癌细胞如何在没有葡萄糖的条件下继续增殖扩张？  

Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms

作　　者：Stefan Burén 

机构地区：[1] Cancer Cell Biology Programme, Growth Factors, Nutrients and Cancer Group, Centro Nacional de Investigaciones Oncológicas, CNIO, Madrid 28029, Spain [2] Biotechnology Programme, Confocal Microscopy Core Unit, Centro Nacional de Investigaciones Oncológicas, CNIO, Madrid 28029, Spain [3] Department of Research Pathology, Cancer Institute, University College London, London WC1E 6JJ, UK [4] Structural Biology and Biocomputing Programme, Spectroscopy and Nuclear Magnetic Resonance Unit, Centro Nacional de Investigaciones Oncológicas, CNIO, Madrid 28029, Spain

出　　处：《现代生物医学进展》2017年第2期I0001-I0002,共2页Progress in Modern Biomedicine

摘　　要：肿瘤细胞最主要的目标就是生存，其甚至不惜破坏其所依附的有机体的健康也要达到生存的目的；为了生存肿瘤细胞会练就许多健康细胞没有的本领，包括在葡萄糖水平极低的情况下继续保持生长势头，而这或许就是常用的抗血管生成因子难以消除癌症的主要原因，肿瘤细胞通常会通过妨碍提供常规的营养物质和葡萄糖的血管的发育来影响机体健康，Cancer cells can adapt and survive under low nutrient conditions, but underlying mechanisms remain poorly explored. We demonstrate here that glucose maintains a functional complex between the co-chaperone URI, PP1γ, and OGT, the enzyme catalyzing O-GlcNAcylation. Glucose deprivation induces the activation of PKA, which phosphorylates URI at Ser-371, resulting in PP1γ release and URI-mediated OGT inhibition. Low OGT activity reduces O-GlcNAcylation and promotes c-MYC degradation to maintain cell survival. In the presence of glucose, PP1γ-bound URI increases OGT and c-MYC levels. Accordingly, mice expressing non-phosphorylatable URI (S371A) in hepatocytes exhibit high OGT activity and c-MYC stabilization, accelerating liver tumorigenesis in agreement with c-MYC oncogenic functions. Our work uncovers that URI-regulated OGT confers c-MYC-dependent survival functions in response to glucose fluctuations.

关 键 词：葡萄糖水 癌细胞 Cell 血管生成因子 增殖 肿瘤细胞 机体健康 营养物质 

分 类 号：Q279[生物学—细胞生物学]