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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2020; 12(6): 448-461
Published online Jun 26, 2020. doi: 10.4252/wjsc.v12.i6.448
Energy metabolism in cancer stem cells
Xuan Zhu, Hui-Hui Chen, Chen-Yi Gao, Xin-Xin Zhang, Jing-Xin Jiang, Yi Zhang, Jun Fang, Feng Zhao, Zhi-Gang Chen
Xuan Zhu, Feng Zhao, Department of Radiation Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
Hui-Hui Chen, The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Hangzhou 310000, Zhejiang Province, China
Hui-Hui Chen, Chen-Yi Gao, Xin-Xin Zhang, Jing-Xin Jiang, Yi Zhang, Zhi-Gang Chen, Department of Breast Surgery, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
Chen-Yi Gao, Xin-Xin Zhang, Jing-Xin Jiang, Yi Zhang, Zhi-Gang Chen, Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
Jun Fang, Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou 310000, Zhejiang Province, China
Author contributions: Zhu X, Chen HH and Gao CY contributed equally to this paper; all authors equally contributed to this paper with conception and design of the study, literature review and analysis, manuscript drafting, critical revision, and editing, and final approval of the final version.
Supported by the National Natural Science Foundation of China, No. 81502564 and No. 81972598; the Natural Science Foundation of Zhejiang Province, No. LY19H160004.
Conflict-of-interest statement: No potential conflicts of interest are reported.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Zhi-Gang Chen, MD, PhD, Assistant Professor, Surgeon, Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, 88 JieFang Road, Hangzhou 310000, Zhejiang Province, China. chenzhigang@zju.edu.cn
Received: February 24, 2020
Peer-review started: February 24, 2020
First decision: April 25, 2020
Revised: May 9, 2020
Accepted: May 19, 2020
Article in press: May 19, 2020
Published online: June 26, 2020
Processing time: 121 Days and 21.1 Hours
Abstract

Normal cells mainly rely on oxidative phosphorylation as an effective energy source in the presence of oxygen. In contrast, most cancer cells use less efficient glycolysis to produce ATP and essential biomolecules. Cancer cells gain the characteristics of metabolic adaptation by reprogramming their metabolic mechanisms to meet the needs of rapid tumor growth. A subset of cancer cells with stem characteristics and the ability to regenerate exist throughout the tumor and are therefore called cancer stem cells (CSCs). New evidence indicates that CSCs have different metabolic phenotypes compared with differentiated cancer cells. CSCs can dynamically transform their metabolic state to favor glycolysis or oxidative metabolism. The mechanism of the metabolic plasticity of CSCs has not been fully elucidated, and existing evidence indicates that the metabolic phenotype of cancer cells is closely related to the tumor microenvironment. Targeting CSC metabolism may provide new and effective methods for the treatment of tumors. In this review, we summarize the metabolic characteristics of cancer cells and CSCs and the mechanisms of the metabolic interplay between the tumor microenvironment and CSCs, and discuss the clinical implications of targeting CSC metabolism.

Keywords: Cancer stem cells; Differentiated cancer cells; Metabolic characteristics; Oxidative phosphorylation; Glycolysis; Tumor microenvironment; Metabolic interplay

Core tip: Accumulating evidence indicates that the inadequacy of many treatments is due to their failure to target cancer stem cells (CSCs). Therefore, CSCs are a promising target for cancer treatment. Recently, it has been reported that CSCs exhibit a unique metabolic phenotype compared to normal cancer cells (non-CSCs), and CSCs can dynamically transform their metabolic state to favor glycolysis or oxidative metabolism. However, the mechanism of the metabolic plasticity of CSCs has not been fully elucidated, and existing evidence indicates that the metabolic phenotype of cancer cells is closely related to the tumor microenvironment (TME). In this article, we summarize the metabolic characteristics of non-CSCs and CSCs, highlight the mechanisms by which CSCs alter their energy metabolism via interactions with the surrounding TME, and discuss the potential therapeutic strategies to target energy metabolism in CSCs.