FIGURE 1 from Antibody–Drug Conjugate αEGFR-E-P125A Reduces Triple-negative Breast Cancer Vasculogenic Mimicry, Motility, and Metastasis through Inhibition of EGFR, Integrin, and FAK/STAT3 Signaling

Elucidating the molecular signaling mechanisms of αEGFR-E-P125A inhibition. A, MDA-MB-231-4175 cells plated in a monolayer (2D), on matrigel (3D), or on matrigel and treated with αEGFR-E-P125A (3D αEGFR-E-P125A). B, Volcano plot depicts 455 total DEGs between 2D and 3D conditions. A total of 153 genes were upregulated while 302 genes were downregulated upon the 2D to 3D transition (left). Heat map depicts the top 100 DEGs between 2D and 3D conditions based on z-score. C, Volcano plot depicts 52 DEGs between 3D and αEGFR-E-P125A conditions. Twenty-nine genes were upregulated while 23 genes were downregulated upon the 3D to αEGFR-E-P125A transition. Heat map depicts all the DEGs from 3D to αEGFR-E-P125A–treated transition based on z-score (right). D, Venn diagram representing the 26 genes from the each of the differentially expressed lists which were identified as being inversely dysregulated upon the induction of VM by matrigel and the inhibition of VM by αEGFR-E-P125A treatment. E, Heat map depicting the log₂FC of the 26 inversely dysregulated genes from 2D to 3D and from 3D to αEGFR-E-P125A treatment transitions. F, GSEA using the Hallmarks gene set depicts inversely related pathways which were upregulated from 2D to 3D and downregulated upon the 3D to αEGFR-E-P125A treatment transition. G, On the basis of the pathways which were identified as being upregulated from 2D to 3D and inversely downregulated from 3D to αEGFR-E-P125A treatment conditions, the top downregulated pathways identified were the IL6-JAK-STAT3 and the angiogenesis signaling pathways.