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Review
. 2022 Jul 13:13:949863.
doi: 10.3389/fphar.2022.949863. eCollection 2022.

ACSL4 as a Potential Target and Biomarker for Anticancer: From Molecular Mechanisms to Clinical Therapeutics

Jun Hou  1   2 , Changqing Jiang  3 , Xudong Wen  4 , Chengming Li  5 , Shiqiang Xiong  1 , Tian Yue  1 , Pan Long  2 , Jianyou Shi  6 , Zhen Zhang  1
Affiliations
Review

ACSL4 as a Potential Target and Biomarker for Anticancer: From Molecular Mechanisms to Clinical Therapeutics

Jun Hou et al. Front Pharmacol. .

Abstract

Cancer is a major public health problem around the world and the key leading cause of death in the world. It is well-known that glucolipid metabolism, immunoreaction, and growth/death pattern of cancer cells are markedly different from normal cells. Recently, acyl-CoA synthetase long-chain family 4 (ACSL4) is found be participated in the activation of long chain fatty acids metabolism, immune signaling transduction, and ferroptosis, which can be a promising potential target and biomarker for anticancer. Specifically, ACSL4 inhibits the progress of lung cancer, estrogen receptor (ER) positive breast cancer, cervical cancer and the up-regulation of ACSL4 can improve the sensitivity of cancer cells to ferroptosis by enhancing the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). However, it is undeniable that the high expression of ACSL4 in ER negative breast cancer, hepatocellular carcinoma, colorectal cancer, and prostate cancer can also be related with tumor cell proliferation, migration, and invasion. In the present review, we provide an update on understanding the controversial roles of ACSL4 in different cancer cells.

Keywords: acyl-CoA synthetase long-chain family; anticancer biomarker; arachidonic acid; ferroptosis; glucolipid metabolism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The brief description of canonical ferroptosis pathway. Cystine enters into cells through the cystine/glutamic acid reverse transporter (System Xc-) and then reduces to cysteine in the glutathione (GSH). GSH acts as a cofactor of glutathione peroxidase 4 (GPX4) to promote the reduction of phospholipid hydroperoxides (PLOOHs) to corresponding alcohols (PLOHs) in cells. Essential lipid peroxidase acyl-CoA synthase long chain family member 4 (ACSL4) and lysophosphatidylcholine acyltransferase (LPCAT) activate PUFA into PUFA-CoA and PUFA-PL, respectively, leading to lipid peroxidation.
FIGURE 2
FIGURE 2
The potential role of ACSL4 in specific immune responses mediated by CD8+ T cells. IFN-γ secreted by CD8+ T cells stimulates ACSL4 and alters tumor cell lipid patterns, thereby increasing the binding of AA in C16 and C18 acyl-chain phospholipids. Lipid peroxidation then leads to ferroptosis of tumor cells.
See this image and copyright information in PMC

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