title: Targeting SREBP-1-driven lipid metabolism to treat cancer.
abstract: 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.
authors.forename: Deliang
authors.initials: D
authors.lastname: Guo
authors.forename: Erica Hlavin
authors.initials: EH
authors.lastname: Bell
authors.forename: Paul
authors.initials: P
authors.lastname: Mischel
authors.affiliation: Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center and Arthur G. James Cancer Hospital, Columbus, OH 43210, USA. deliang.guo@osumc.edu.
authors.forename: Arnab
authors.initials: A
authors.lastname: Chakravarti
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D050155:Lipogenesis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D011973:Receptors, LDL / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D011973:Receptors, LDL; D051780:Sterol Regulatory Element Binding Protein 1; D018698:Glutamic Acid; D002784:Cholesterol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt