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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Nov 26, 2020; 12(11): 1307-1326
Published online Nov 26, 2020. doi: 10.4252/wjsc.v12.i11.1307
Stem cell quiescence and its clinical relevance
Meng Luo, Jin-Fan Li, Qi Yang, Kun Zhang, Zhan-Wei Wang, Shu Zheng, Jiao-Jiao Zhou
Meng Luo, Kun Zhang, Jiao-Jiao Zhou, Department of Breast Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Meng Luo, Shu Zheng, Jiao-Jiao Zhou, Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Jin-Fan Li, Qi Yang, Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Zhan-Wei Wang, Department of Breast Surgery, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou 313003, Zhejiang Province, China
Author contributions: Luo M, Li JF, and Yang Q wrote parts of the manuscript; Zhang K and Wang ZW prepared the table and figures; Zhou JJ and Zheng S participated in the conception and revised the manuscript.
Supported by the National Natural Science Foundation of China, No. 81702866.
Conflict-of-interest statement: All authors have nothing to disclose.
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: Jiao-Jiao Zhou, MD, PhD, Doctor, Occupational Physician, Surgeon, Department of Breast Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China. zhoujj@zju.edu.cn
Received: July 10, 2020
Peer-review started: July 10, 2020
First decision: July 30, 2020
Revised: August 28, 2020
Accepted: September 22, 2020
Article in press: September 22, 2020
Published online: November 26, 2020
Processing time: 139 Days and 4.5 Hours
Abstract

Quiescent state has been observed in stem cells (SCs), including in adult SCs and in cancer SCs (CSCs). Quiescent status of SCs contributes to SC self-renewal and conduces to averting SC death from harsh external stimuli. In this review, we provide an overview of intrinsic mechanisms and extrinsic factors that regulate adult SC quiescence. The intrinsic mechanisms discussed here include the cell cycle, mitogenic signaling, Notch signaling, epigenetic modification, and metabolism and transcriptional regulation, while the extrinsic factors summarized here include microenvironment cells, extracellular factors, and immune response and inflammation in microenvironment. Quiescent state of CSCs has been known to contribute immensely to therapeutic resistance in multiple cancers. The characteristics and the regulation mechanisms of quiescent CSCs are discussed in detail. Importantly, we also outline the recent advances and controversies in therapeutic strategies targeting CSC quiescence.

Keywords: Stem cell; Cancer stem cell; Quiescence; Targeting quiescence

Core Tip: Quiescent state is very important for both adult stem cells and cancer stem cells. Quiescence of adult stem cells is regulated by multiple intrinsic mechanisms and extrinsic factors. Quiescence of cancer stem cells contributes immensely to therapeutic resistance in multiple cancers. Targeting the quiescence of cancer stem cells may be a novel strategy in clinical practice.