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. 2021 Apr 22;11:669250. doi: 10.3389/fonc.2021.669250

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Copyright © 2021 Mohan, Raj R., Mohan, K. P. and Maliekal

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The regulation of Metastatic CSCs. Different signaling pathways activate ALDH1A1, OCT4 and SOX2, which activates β-catenin to induce EMT. At the same time OCT4/SOX2 regulates EMT in a β-catenin independent way also. NANOG inhibits β-catenin, but activates EMT through other pathway. When there is induction of EMT, epithelial cells might acquire stemness and metastatic ability, and gradually lose the stemness. The hybrid cells showing stemness property and metastatic property together are the metastasis initiating cells (MICs).