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. 2021 Mar 17;40:102. doi: 10.1186/s13046-021-01908-8

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© The Author(s) 2021

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 — FN1 as player in metastatic process and as diagnostic and therapeutic target. At the primary tumor site, the cancer cells and cancer associated fibroblasts (CAFs) deposit FN1. FN1 activates intracellular signaling, mediated by integrins, TLRs, Wnt/β catenin, and P13K, that lead to an increase of expression and secretion of FN1, MMPs, TGFβ. In parallel, FN1 is transferred by EVs. Cancer cells, with invasive capabilities, extravasate and reach a secondary organ, where tumor dormancy immune controlled may occur. Dormancy escape arises in the metastatic outgrowth in a permissive microenvironment with FN1 and collagen enriched ECM, affecting resistance to therapy. EDB isoform of FN1 is used as a biomarker for cancer diagnostic imaging and FN1 pathway as a target for therapeutic applications. Created with BioRender.com