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. 2020 May 15;11:2416. doi: 10.1038/s41467-020-16199-4

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© The Author(s) 2020

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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Fig. 1 — a Schematic representation of developing doxorubicin resistance in mice using the TNBC cell line, MDA-MB-231 (left panel). Tumor volume fold change (log2) of vehicle-treated, doxorubicin-sensitive and -resistant tumors (right panel). Clipart reprinted with permission from Springer Nature, Nature Protocols, FACS isolation of endothelial cells and pericytes from mouse brain microregions, Elizabeth E Crouch and Fiona Doetsch, Copyright 2018. b Tumor volumes of vehicle (n = 8), sensitive (n = 12) and -resistant (n = 6) tumors. c Waterfall plot of tumor volume fold change over time. Asterisk indicates tumors profiled by RNA-Seq. V vehicle; S sensitive; and R resistant. d Kaplan–Meier survival curve representing the percentage overall survival (OS) in chemotherapy-treated TNBC patients (n = 106) based on low vs. high (median) DoxoR-GS score. e Summary of IPA analysis showing top deregulated pathways in doxorubicin-resistant xenografts. f Genes associated with focal adhesion signaling are enriched in tumors of high DoxoR-GS scorers from GSE58812. g Expression of integrin alpha 5 (ITGA5) in doxorubicin-sensitive (n = 8) vs. -resistant (n = 6) xenografts at mRNA (left) and protein (right) levels, demonstrating membranous and cytoplasmic staining. h Kaplan–Meier survival curve representing the percentage relapse-free survival (RFS) in chemotherapy-treated basal patients (n = 132) based on low vs. high ITGA5 (median) expression. i Table summarizing association of ITGA5 with survival in patients of different subtypes that received or did not receive chemotherapy. j Expression of fibronectin (FN1) in doxorubicin-sensitive (n = 12) vs. resistant (n = 12) tumors at mRNA (left) and protein (right) levels, demonstrating mild to moderate cytoplasmic staining. k Kaplan–Meier survival curve representing the percentage RFS in chemotherapy-treated basal breast cancer patients (n = 132) based on low vs. high FN1 (median) expression. l Table summarizing association of FN1 with survival in patients of different subtypes that received or did not receive chemotherapy. Data on b represent mean ± SEM and all others represent mean ± SD. In Box plots, the box depicts median, 25th to 75th percentiles, and the whisker depicts min to max for this figure and all others. Two-sided Student’s t-test was used to calculate statistical difference between two groups. Significance for survival analyses was calculated by log-rank (Mantel-Cox) test. NES Normalized enrichment score, HR hazard ratio. Scale bar = 100 µm for g, j. Source data are provided as a Source data file.