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. 2021 Sep 4;12(9):835. doi: 10.1038/s41419-021-04116-6

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — Quiescent CSCs are induced and maintained by different TME components, including a hypoxic tumor environment, laminins, and matrix stiffness of the ECM and CAFs. Quiescent CSCs can reprogram their metabolism to flexibly adapt to environmental changes, which is considered crucial for them to enhance the antioxidant compensative capacity and induce chemotherapy resistance. And it is a promising strategy of making them susceptive to chemotherapies through inhibition of their metabolic flexibility.