title: Lipid desaturation - the next step in targeting lipogenesis in cancer?
abstract: Metabolic reprogramming is a central feature of transformed cells. Cancer metabolism is now fully back in the focus of cancer research, as the interactions between oncogenic signalling and cellular metabolic processes are uncovered. One aspect of metabolic reprogramming in cancer is alterations in lipid metabolism. In contrast to most untransformed tissues, which satisfy their demand from dietary lipids, cancer cells frequently re-activate de novo lipogenesis. However, compounds targeting fatty acid synthase (FASN), a multiprotein complex integral to lipogenesis, have so far shown limited efficacy in pre-clinical cancer models and to date only one FASN inhibitor has entered clinical trials. Recently, a number of studies have suggested that enhanced production of fatty acids in cancer cells could also increases their dependence on the activity of desaturases, a class of enzymes that insert double bonds into acyl-CoA chains. Targeting desaturase activity could provide a window of opportunity to selectively interfere with the metabolic activity of cancer cells. This review will summarise some key findings that implicate altered lipid metabolism in cancer and investigate the molecular interactions between lipid desaturation and cancer cell survival.
authors.affiliation: The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK.
authors.forename: Barrie
authors.initials: B
authors.lastname: Peck
authors.affiliation: Department of Biochemistry and Molecular Biology, Theodor-Boveri-Institute, Wuerzburg, Germany.|Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
authors.forename: Almut
authors.initials: A
authors.lastname: Schulze
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015687:Cell Hypoxia; D059865:Endoplasmic Reticulum Stress; D005227:Fatty Acids / Q000096:biosynthesis; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000502:physiology; D050155:Lipogenesis / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051779:Sterol Regulatory Element Binding Proteins / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D005227:Fatty Acids; D008055:Lipids; D051779:Sterol Regulatory Element Binding Proteins; D013230:Stearoyl-CoA Desaturase
keywords: SCD; cancer; hypoxia; lipid desaturation; lipid synthesis; metabolism; microenvironment