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. 2020 Apr 27;27(10):2768–2780. doi: 10.1038/s41418-020-0541-0

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© The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare 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. 4 — a Schematic of death receptor cell death signaling pathway. Effect of Smac-mimetic (SM)-induced inhibition of IAPs (red inhibitory arrows) and -induced formation of cell death complex (black arrow) are shown. b List of selected genes and their protein names that influence Smac-mimetic-induced cell death. c Most Smac-mimetic killing genes are upregulated in TCGA TNBC samples compared with ER⁺ cancers (n = 132 for ER⁺ and n = 183 for TNBC, p = 0.0005) but a minority are downregulated. The plot shows −log10 p value and the direction of change for each gene in TNBC versus ER⁺ samples. d Box plots representing the expression of indicated genes in PDX models (top panels, n = 3 for ER⁺ and n = 7 for TNBC PDX models), in TCGA samples (middle panels, n = 132 for ER⁺ and n = 183 for TNBC samples) and in METABRIC samples (bottom panels, n = 492 for ER⁺ and n = 331 for TNBC samples). e Cell viability assessed by measurement of PI negative cells by flow cytometry of indicated breast cancer cell lines treated for 24 h with 1 μM of birinapant or 100 ng/ml of TNF or combination of both. Data are means ± SD; n = 2–3 independent experiments. f Cell viability assessed using CellTiter-Glo of ER⁺ PDX tumor cells treated for 24 h with 1 μM of birinapant or 10 ng/ml or 100 ng/ml of TNF (indicated as TNF 10 or TNF 100, respectively) or combination of birinapant with either TNF concentrations. Data are means ± SD; n = 3–5 independent tumors. e, f Each dot represents either an independent tumor or an independent experiment.