Fig. 4 |. HDACs 3 and 8 regulate the stiffness-induced tumorigenic phenotype.

a, String-DB protein-protein interaction network of top ten interactors with Sp1. b, Confocal immunofluorescence of shHDAC1, shHDAC2, shHDAC3, and shHDAC8 cells in stiff matrices (top, from at least 12 total images per group) and representative outlines of clusters (bottom). Scale bars represent 100 μm. c, Quantification of roundness for HDAC knockdowns in stiff matrices compared to empty vector controls in soft or stiff matrices and SAHA-treated cells in stiff matrices (n = 3, median ± 95% C.I.). d, Quantification of invasive clusters (n = 3, mean ± S.D.). e, Schematic timeline of small molecule inhibitor of Sp1 washout experiment. f, Confocal immunofluorescence of cells in soft or stiff matrices treated for the duration indicated and imaged after 14 total days (representative images from 15 images per group). g, Quantification of roundness of cell clusters in soft or stiff matrices treated with SAHA or vehicle control for the indicated period of time (n = 3, median ± 95% C.I.). h, Quantification of invasive clusters (n = 3, mean ± S.D.). i, Schematic illustrating sequential events from ECM mechanical properties to phenotype via mechanically-induced chromatin remodeling. Significance was determined by Kruskal-Wallis test followed by Dunn’s multiple testing correction for roundness and by one-way ANOVA followed by Dunnett’s multiple testing correction for invasion.