Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Feb 26, 2022; 14(2): 146-162
Published online Feb 26, 2022. doi: 10.4252/wjsc.v14.i2.146
Abnormal lipid synthesis as a therapeutic target for cancer stem cells
Si-Yu Wang, Qin-Chao Hu, Tong Wu, Juan Xia, Xiao-An Tao, Bin Cheng
Si-Yu Wang, Qin-Chao Hu, Tong Wu, Juan Xia, Xiao-An Tao, Bin Cheng, Department of Oral Medicine, Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China
Si-Yu Wang, Qin-Chao Hu, Tong Wu, Juan Xia, Xiao-An Tao, Bin Cheng, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China
Author contributions: Wang SY was responsible for conceptualizing this review and writing the original draft; Hu QC was involved in the conceptualization, funding acquisition, and review and editing of the manuscript; Wu T participated in the conceptualization and review of the manuscript; Tao XA, Xia J, and Cheng B contributed to the editing, improving, and finalizing of the manuscript; all authors approved the final version of the manuscript and agreed to be accountable for this work.
Supported by the National Natural Science Foundation of China, No. 82001044 and No. 81630025; the China Postdoctoral Science Foundation, No. 2020M673019; the Guangdong Basic and Applied Basic Research Foundation, No. 2019A1515110071; and the Natural Science Foundation of Guangdong Province, No. 2017A030311033.
Conflict-of-interest statement: The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bin Cheng, MD, PhD, Dean, Department of Oral Medicine, Hospital of Stomatology, Sun Yat-sen University, No. 56 Lingyuanxi Road, Guangzhou 510000, Guangdong Province, China. chengbin@mail.sysu.edu.cn
Received: March 16, 2021
Peer-review started: March 16, 2021
First decision: May 5, 2021
Revised: May 19, 2021
Accepted: February 14, 2022
Article in press: February 14, 2022
Published online: February 26, 2022
Abstract

Cancer stem cells (CSCs) comprise a subpopulation of cancer cells with stem cell properties, which exhibit the characteristics of high tumorigenicity, self-renewal, and tumor initiation and are associated with the occurrence, metastasis, therapy resistance, and relapse of cancer. Compared with differentiated cells, CSCs have unique metabolic characteristics, and metabolic reprogramming contributes to the self-renewal and maintenance of stem cells. It has been reported that CSCs are highly dependent on lipid metabolism to maintain stemness and satisfy the requirements of biosynthesis and energy metabolism. In this review, we demonstrate that lipid anabolism alterations promote the survival of CSCs, including de novo lipogenesis, lipid desaturation, and cholesterol synthesis. In addition, we also emphasize the molecular mechanism underlying the relationship between lipid synthesis and stem cell survival, the signal trans-duction pathways involved, and the application prospect of lipid synthesis reprogramming in CSC therapy. It is demonstrated that the dependence on lipid synthesis makes targeting of lipid synthesis metabolism a promising therapeutic strategy for eliminating CSCs. Targeting key molecules in lipid synthesis will play an important role in anti-CSC therapy.

Keywords: Lipid synthesis, Cancer stem cells, Anti-cancer therapy, Stem cell survival, Lipid anabolism

Core Tip: Cancer stem cells (CSCs) are associated with the occurrence, metastasis, therapy resistance, and relapse of cancer. CSCs are highly dependent on lipid metabolism to maintain stemness and satisfy the requirements of biosynthesis and energy metabolism. Here, we review the molecular mechanism underlying the relationship between lipid synthesis and stem cell survival, the signal transduction pathways involved, and the application prospect of lipid synthesis reprogramming in CSC therapy. We demonstrate that lipid anabolism alterations promote the survival of CSCs.