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. 2019 Feb 8;26(11):2223–2236. doi: 10.1038/s41418-019-0289-6

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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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Fig. 7 — TS regulates de-differentiated tumor phenotype via DPYD-mediated thymidine catabolism. a Scheme of the thymidylate catabolic pathway. b DPYD (p = 0.0031) and NT5E (p = 0.0001) mRNA expression levels in epithelial and mesenchymal BC cell lines (CCLE dataset). The statistical tests are unpaired two tailed t-test. c Western blot quantification of DPYD knockdown in MDA-MB-231, and the effects on (d) CD44/CD24 profile and e migratory ability (p < 0.0001, two-way ANOVA, Sidak’s multiple comparison). f FACS plots of MDA-MB-231 cells with DPYD knockdown overexpressing TS or an empty vector and stained with CD44/CD24. g Sphere counts for shTS#1 cells in MDA-MB-231 (p < 0.0394 between pLKO and NT, p < 0.0001 between NT and DHT) and BT-549 (p < 0.0001 between pLKO and NT, p = 0.0023 between NT and DHT, one-way ANOVA, Turkey’s multiple comparison) after treatment with 1 µM dihydrothymine (DHT). NT (DMSO) is the non-treated control. h CD24/44 profile showing the effect of 10 µM DHT on CD24⁺ population in MDA-MB-231 cells with TS knock-down. Points are avg ± S