Figure 4. YAP regulates focal adhesion/cytoskeleton integrity downstream of RhoA.
(a) Heatmap representing the RNA expression levels by normalized ΔCt values obtained in two qRT–PCR independent replicates of YAP mutant clone C3 as compared with CAL51 WT. (b) Graph: barplot representing mean value±s.d. of up- and downregulated genes with a fold change higher than 2.0 in YAP mutant clone C3 as compared to CAL51 WT. (c) Western blot analysis of the indicated focal adhesion (FA) proteins; n=3. (d) Representative confocal images of WT CAL51 and YAP mutant clones C2a and C3, showing vinculin staining (green). (e) Protein analysis of the indicated cytoskeleton- and FA-associated proteins in WT CAL51 and YAP mutant clones; n=3. (f) Graphs: quantification of cell contact area and Young's Modulus in WT CAL51 and YAP-defective clone C3. Values are shown as median±min/max (n=24, 3 technical replicates, Welch's t-test, ***P<0.001 and **** P<0.0001,). (g) Box: Representative brightfield image of WT CAL51 and C3 clone migrated through ECM-coated transwell membrane (8 μm) and stained with crystal violet after 24 h, quantification is shown in the upper graph. The data represent the mean value±s.d. (12 random fields, 2 technical replicates, **P<0.01 and ***P<0.001, Kruskal–Wallis test followed by post hoc Dunn‘s test). Bottom: qRT–PCR array analysis of genes involved in ECM remodelling in YAP mutant cells (C3) as compared with the control. The threshold was set at 2.0. Right: Representative brightfield image of CAL51 WT and YAP mutant cells C3 grown in three-dimensional (3D) Matrigel for 120 h. (h) Representative confocal images showing the arrangement of F-actin in WT Cal51 and mutant clones C2a and C3 stained with Alexa Fluor 546 Phalloidin. (i) Representative western blot quantification of G-actin/F-actin ratio in WT CAL51 and YAP mutant clones. (j) Representative western blot analysis of the indicated proteins; n=3. (k) Representative confocal image of WT CAL51 cell transfected with EGFP-RhoA-Q63L and stained with anti-YAP antibody (red), Alexa Fluor 647 Phalloidin (white). Image analysis shows the nuclear/cytoplasmic distribution of YAP protein in non-transfected and transfected cells. (l) Confocal images of WT CAL51 and mutant clone C3 transfected with EGFP-RhoA-Q63L and stained with anti-vinculin antibody (red), Alexa Fluor 647 Phalloidin (white).