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. 2019 May 29;9:8028. doi: 10.1038/s41598-019-44361-6

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© The Author(s) 2019

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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Proposed model describing the paracrine loop existing between anaplastic thyroid tumor cells and stromal fibroblasts in TC. Soluble signals derived from ATC cells promotes the up-regulation of pSrc and pAkt in human fibroblasts, leading to increased cell proliferation, secretory functions and metabolic reprogramming of fibroblasts, consistent with the induction of CAF phenotype. Moreover, CM from activated fibroblasts promoted thyroid cell proliferation and invasion, thereby increasing TC progression.