甾醇调节元件结合蛋白
脂质代谢
谷氨酰胺分解
PI3K/AKT/mTOR通路
生物
癌症研究
低密度脂蛋白受体
下调和上调
脂肪酸合成
细胞生物学
信号转导
癌症
癌细胞
化学
新陈代谢
转录因子
生物化学
糖酵解
脂蛋白
脂肪酸
胆固醇
基因
遗传学
作者
Deliang Guo,Erica H. Bell,Paul S. Mischel,Arnab Chakravarti
标识
DOI:10.2174/13816128113199990486
摘要
Metabolic reprogramming is a hallmark of cancer. Oncogenic growth signaling regulates glucose, glutamine and lipid metabolism to meet the bioenergetics and biosynthetic demands of rapidly proliferating tumor cells. Emerging evidence indicates that sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor that controls lipid metabolism, is a critical link between oncogenic signaling and tumor metabolism. We recently demonstrated that SREBP-1 is required for the survival of mutant EGFR-containing glioblastoma, and that this pro-survival metabolic pathway is mediated, in part, by SREBP-1-dependent upregulation of the fatty acid synthesis and low density lipoprotein (LDL) receptor (LDLR). These results have identified EGFR/PI3K/Akt/SREBP-1 signaling pathway that promotes growth and survival in glioblastoma, and potentially other cancer types. Here, we summarize recent insights in the understanding of cancer lipid metabolism, and discuss the evidence linking SREBP-1 with PI3K/Akt signaling-controlled glycolysis and with Myc-regulated glutaminolysis to lipid metabolism. We also discuss the development of potential drugs targeting the SREBP-1- driven lipid metabolism as anti-cancer agents.
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