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. 2022 Sep 8;15:129. doi: 10.1186/s13045-022-01347-8

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© The Author(s) 2022

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — Role of EMT in the tumor metastasis. Tumor cells in situ are induced by EMT to initiate the metastatic cascade process. Intermediate state and mesenchymal stem cells (MCSCs) lose intercellular junctions, detach from tumor tissue, and invade surrounding tissues. Metastatic tumor cells enter the circulation through the endothelial barrier by active or passive trans-endothelial migration (TEM), invading the surrounding mesenchyme and disrupting endothelial junctions. After entering the circulation, single or clustered circulating tumor cells (CTCs) can bind to coagulation factors on platelets by expressing thrombin, forming a unique immune mechanism that protects metastatic cells from immune escape. Neutrophils are also recruited and bind to CTCs to promote tumor cells survival and proliferation. CTCs move slowly, roll along the endothelium, and then arrest. MCSCs anchor with endothelial cells for extravasation and then colonize distal organs via the MET process