Targeting SREBP-1-driven lipid metabolism to treat cancer.
Targeting SREBP-1-driven lipid metabolism to treat cancer.
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DOI：
10.2174/13816128113199990486
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发表时间：
2014
影响因子：
3.1
通讯作者：
Chakravarti A
中科院分区：
文献类型：
--
作者：
Guo D;Bell EH;Mischel P;Chakravarti A
代谢重编程是癌症的标志。致癌生长信号调节葡萄糖、谷氨酰胺和脂质代谢以满足快速增殖的肿瘤细胞的生物能量学和生物合成需求。新的证据表明，固醇调节元件结合蛋白1（SREBP-1），一个主转录因子，控制脂质代谢，是致癌信号和肿瘤代谢之间的关键环节。我们最近证明，SREBP-1是需要突变EGFR的胶质母细胞瘤的生存，这种促生存代谢途径介导的，部分是由SREBP-1依赖性上调脂肪酸合成和低密度脂蛋白（LDL）受体（LDLR）。这些结果已经确定了EGFR/PI 3 K/Akt/SREBP-1信号通路，其促进胶质母细胞瘤以及潜在的其他癌症类型的生长和存活。在这里，我们总结了最近的见解，在癌症脂质代谢的理解，并讨论了证据SREBP-1与PI 3 K/Akt信号控制的糖酵解和Myc调节的β-氨基糖苷酶的脂质代谢。我们还讨论了潜在的药物靶向SREBP-1驱动的脂质代谢作为抗癌剂的发展。
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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影响因子：
29
作者：
Babic I;Anderson ES;Tanaka K;Guo D;Masui K;Li B;Zhu S;Gu Y;Villa GR;Akhavan D;Nathanson D;Gini B;Mareninov S;Li R;Camacho CE;Kurdistani SK;Eskin A;Nelson SF;Yong WH;Cavenee WK;Cloughesy TF;Christofk HR;Black DL;Mischel PS
通讯作者：
Mischel PS
雷帕霉素在I期试验中针对复发性PTEN缺陷型胶质母细胞瘤患者的抗肿瘤活性。
影响因子：
15.8
作者：
Cloughesy, Tim F.;Yoshimoto, Koji;Nghiemphu, Phioanh;Brown, Kevin;Dang, Julie;Zhu, Shaojun;Hsueh, Teli;Chen, Yinan;Wang, Wei;Youngkin, David;Liau, Linda;Martin, Neil;Becker, Don;Bergsneider, Marvin;Lai, Albert;Green, Richard;Oglesby, Tom;Koleto, Michael;Trent, Jeff;Horvath, Steve;Mischel, Paul S.;Mellinghoff, Ingo K.;Sawyers, Charles L.
通讯作者：
Sawyers, Charles L.
影响因子：
3.8
作者：
Chinot, O. L.;Rouge, T. de la Motte;Cloughesy, T.
通讯作者：
Cloughesy, T.
影响因子：
56.9
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
影响因子：
8
作者：
Bauer, DE;Hatzivassiliou, G;Thompson, CB
通讯作者：
Thompson, CB