论文部分内容阅读
TP53诱导的糖酵解和凋亡调节因子(TP53-induced glycolysis and apoptosis regulator,TIGAR)是p53下游的直接靶基因,其编码蛋白能够降解2,6-二磷酸果糖,后者是肿瘤细胞糖酵解途径中关键酶6-磷酸果糖激酶1(6-phosphofructokinase 1,PFK1)的最强激活剂,从而对糖酵解产生抑制作用。TIGAR可促使糖代谢更多地流向磷酸戊糖途径(pentose phosphate pathway,PPP),促进烟酰胺腺嘌呤二核苷酸磷酸(nicotinamide adenine dinucleotide phosphate,NADPH)和谷胱甘肽(glutathione,GSH)的产生,降低细胞内活性氧(reactive oxygen species,ROS)水平。因此,TIGAR是维持肿瘤细胞氧化还原状态平衡的重要因子,对细胞凋亡起到重要的调节作用。最新研究表明,TIGAR在肿瘤发生、进展及转移过程中发挥重要作用,而且干扰TIGAR表达可以提高多种肿瘤细胞对放化疗的敏感性,提示TIGAR可能成为一个极具潜力的肿瘤治疗靶点。本文对近年来TIGAR在肿瘤发生、进展和转移中的作用以及其靶向治疗的研究进展进行简要综述。
TP53-induced glycolysis and apoptosis regulator (TIGAR), a direct target of p53 downstream, encodes a protein that degrades fructose-2,6-diphosphate, the latter being a tumor cell glycoprotein The most potent activator of 6-phosphofructokinase 1 (PFK1), a key enzyme involved in the pathway, inhibits glycolysis. TIGAR can promote more glucose metabolism to the pentose phosphate pathway (PPP), promote nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) Produce and reduce the level of intracellular reactive oxygen species (ROS). Therefore, TIGAR is an important factor in maintaining the balance of the redox state of tumor cells and plays an important regulatory role in apoptosis. Recent studies have shown that TIGAR plays an important role in tumorigenesis, progression and metastasis. Interference with TIGAR expression can increase the sensitivity of various tumor cells to radiotherapy and chemotherapy, suggesting that TIGAR may be a potential tumor target. This article briefly reviews the role of TIGAR in tumorigenesis, progression and metastasis in recent years and the progress of its targeted therapy.