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. 2019 Mar 4;9:3395. doi: 10.1038/s41598-018-37625-0

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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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Correlation between TReD and molecular signature. (A) EGFR diffusivity versus luminal differentiation score. The luminal differentiation scores, as calculated on the basis of UNC337 gene expression database, represent the differentiation potentials of breast cells in a luminal epithelial differentiation lineage from mammary stem cells (MaSCs) to the luminal progenitor cells, and eventually to mature luminal cells. (B) The negative correlation between EGFR diffusivity and luminal differentiation score was seen, with the Pearson correlation coefficient r = −0.75. (C) Heat map generated from Genevestigator, showing the expression potential of the 28 genes related to EMT and the five breast cancer cell subtypes (luminal A, luminal B, HER2-rich, basal, and claudin-low). The highly invasive cancer cells exhibit features of mesenchymal cells. As higher EGFR diffusivities were observed in the highly invasive cells (MDA-MB-231 and BT549), we speculated that the EMT might alter the EGFR dynamics. Each cell subtype and the corresponding biomarkers have the same color code, and the colored boxes highlight the differences in molecular signatures among these seven cell lines. The CLDN genes are the biomarkers for claudin-low cells but also the EMT-downregulated genes.