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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Bibliographic Details
Published in:The FEBS journal Vol. 283; no. 15; pp. 2767 - 2778
Main Authors: Peck, Barrie, Schulze, Almut
Format: Journal Article
Language:English
Published: England Blackwell Publishing Ltd 01.08.2016
Subjects:
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
Online Access:Get full text
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Summary: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.
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ISSN:1742-464X
1742-4658
DOI:10.1111/febs.13681