Liu, Jorlin;
Waugh, Mark G;
(2023)
The regulation and functions of ACSL3 and ACSL4 in the liver and hepatocellular carcinoma.
Liver Cancer International
, 4
(1)
pp. 28-41.
10.1002/lci2.68.
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Abstract
Hepatocellular carcinoma (HCC) is a heterogeneous disease that often features dysregulated tumour lipid metabolism. ACSL3 and ACSL4 are two homologous long chain acyl-coenzyme A synthetases (ACSL) that preferentially catalyse the activation of monounsaturated and polyunsaturated fatty acids, respectively. Both enzymes are frequently overexpressed in HCC, and multiple reports have implicated ACSL4 in tumour progression. Increased expression of these isozymes in tumour cells can upregulate lipid metabolism through de novo lipogenesis, fatty acid β-oxidation and acyl chain remodelling of membrane phospholipids. We describe the subcellular functions of ACSL3 and ACSL4 in hepatocytes, and the transcriptional, epigenetic and post-translational mechanisms underpinning their regulation. We discuss the evidence that these enzymes can modulate hepatocarcinogenic signalling by oncoproteins, cell death by apoptosis or ferroptosis, and protein degradation through the ubiquitin-proteasome pathway. In addition, we survey how knowledge in this area may inform new approaches to the diagnosis and treatment of HCC and deepen our understanding of how lipid metabolic reprogramming can promote hepatic tumour growth.
| Type: | Article |
|---|---|
| Title: | The regulation and functions of ACSL3 and ACSL4 in the liver and hepatocellular carcinoma |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/lci2.68 |
| Publisher version: | https://doi.org/10.1002/lci2.68 |
| Language: | English |
| Additional information: | Copyright © 2022 The Authors. Liver Cancer International published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | ACSL3, ACSL4, ferroptosis, hepatocellular carcinoma, lipid metabolism, liver |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10159384 |
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