Lipid desaturation – the next step in targeting lipogenesis in cancer?

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 l...

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Vydáno v:	The FEBS journal Ročník 283; číslo 15; s. 2767 - 2778
Hlavní autoři:	Peck, Barrie, Schulze, Almut
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Blackwell Publishing Ltd 01.08.2016
Témata:	acyl coenzyme A Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Cancer cell communication Cell Hypoxia cell viability clinical trials dietary fat Endoplasmic Reticulum Stress Fatty acids Fatty Acids - biosynthesis fatty-acid synthase Humans hypoxia lipid desaturation Lipid Metabolism lipid synthesis Lipids Lipids - physiology lipogenesis Lipogenesis - drug effects Metabolism microenvironment multiprotein complexes neoplasm cells neoplasms Neoplasms - drug therapy Neoplasms - enzymology Neoplasms - metabolism SCD Stearoyl-CoA Desaturase - antagonists & inhibitors Stearoyl-CoA Desaturase - metabolism Sterol Regulatory Element Binding Proteins - physiology tissues microenvironment hypoxia lipid synthesis SCD lipid desaturation cancer metabolism
ISSN:	1742-464X, 1742-4658
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Popis
Shrnutí:	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. Lipids have important structural roles and are essential for many cellular functions. While most normal tissues rely mainly on dietary lipids, many cancers show increased rates of lipid biosynthesis, making this process an attractive therapeutic target. Here we review evidence supporting the essential role for stearoyl‐CoA desaturase, which generates mono‐unsaturated fatty acids, in maintaining lipid provision in cancer cells.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-3 content type line 23 ObjectType-Review-1
ISSN:	1742-464X 1742-4658
DOI:	10.1111/febs.13681