Figure 4 from Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor–Positive Breast Cancer
Year: 2023
Type: other
Abstract: Estrogen deprivation upregulates IFNγ response through NF-κB signaling. A, RNA-seq analysis of MCF-7 cells grown in HD conditions or in the presence of E2 for three days. The volcano plot shows genes differently expressed between HD- and E2-treated conditions (log2FC>1, Padj < 0.01). Number on the top shows the total number of genes differentially expressed for each condition. B, GSEA of upregulated pathways in E2-stimulated cells. C, GSEA of upregulated pathways in the HD condition. D, Three-cluster K-means plot of genes without and with IFNγ stimulation at different time points in cells grown in HD or E2 conditions with and without E2 for three days. E–G, Hallmark pathway analysis of “E2-induced” genes (E), “IFNγ early” (F), and “IFNγ late” (FDR < 0.05; G). H, Supervised heat map of the expression of IFNγ and antigen presentation-related genes in E2-treated and HD condition without and with IFNγ treatment. I–J, ATAC-seq that was performed in MCF7 cells grown in the presence or absence of E2 for 48 hours and followed by ± IFNγ 10 ng/mL stimulation for 24 hours. I, Tornado plots of chromatin accessibility sites based on ATAC-seq showing accessible sites significantly different between E2 and HD conditions showing IFNγ-treated or no IFNγ-treated conditions. J, Tornado plots showing the chromatin sites accessibly induced by IFNγ stimulation in E2 versus HD conditions. K, Motifs enriched in the chromatin accessible sites in J.
Authors: Francisco Hermida-Prado, Yingtian Xie, Shira Sherman, Zsuzsanna Nagy, Douglas Russo, Tara Akhshi, Zhengtao Chu, Avery Feit, Marco Campisi, Minyue Chen, Agostina Nardone, Cristina Guarducci, Klothilda Lim, Alba Font-Tello, Irene Lee, Juana García-Pedrero, Israel Cañadas, Judith Agudo, Ying Huang, Tal Sella, Qingchun Jin, Nabihah Tayob, Elizabeth A. Mittendorf, Sara M. Tolaney, Xintao Qiu, Henry Long, William F. Symmans, Jia-Ren Lin, Sandro Santagata, Isabelle Bedrosian, Denise A. Yardley, Ingrid A. Mayer, Edward T. Richardson, Giacomo Oliveira, Catherine J. Wu, Eugene F. Schuster, Mitch Dowsett, Alana L. Welm, David Barbie, Otto Metzger, Rinath Jeselsohn
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4387263987