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. 2022 Apr 21;13(4):394. doi: 10.1038/s41419-022-04848-z

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© The Author(s) 2022

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. 4 — The process of retrodifferentiation includes EMT and metabolic reprogramming of non-CSC cells. Additionally, activation of PKA can induce MET in CSCs and lead to the loss of tumor-initiating ability in CSCs. CSCs cancer stem cells, EMT epithelial–mesenchymal transition, MET mesenchymal-to-epithelial transition, CAFs cancer-associated fibroblasts, TANs tumor-associated neutrophils, TAMs tumor-associated macrophages, HSCs hepatic stellate cells, MDSCs myeloid-derived suppressor cells, PKA protein kinase A.