Figure 2.

SRC inhibition reduces YAP/TAZ transcriptional activity and target gene expression. A, A375 cells stably expressing control empty vector, WT SRC, SRC^Y527F, or dasatinib-resistant forms of WT SRC (SRC^T338I) or SRC^Y527F (SRC^Y527F,T338I) were assayed for YAP/TAZ-TEAD transcriptional activity following 6.5-h treatment with the indicated dose of dasatinib (n = 3 independent experiments). B, A735 cells were treated with DMSO or 500 nm dasatinib for 6.5 h and then assayed by qPCR. C, A735 cells stably expressing either a control or an SRC shRNA (pRetroSuper-shSRC) were assayed by Western blotting and for YAP/TAZ-TEAD transcriptional activity. Note that both lanes were from the same blot but were not adjacent. D–F, the indicated cell lines were treated with DMSO, 500 nm dasatinib (D and F), or 100 nm dasatinib (E) for 6.5 h and then assayed by qPCR (D) or for YAP/TAZ-TEAD transcriptional activity (E and F). Scatter plots show mean ± S.D. (error bars), where each dot is an independent experiment in which the dasatinib-treated cells (B and D–F) or SRC shRNA cells (C) were converted to -fold change from control cells, which are indicated by the red dotted line. Statistical significance was tested using two-way ANOVA with Dunnett's multiple-comparison test (A) and Student's t test (B–F). n.s., p > 0.05; *, p ≤ 0.05; **, p ≤ 0.01; ***, p ≤ 0.001; ****, p ≤ 0.0001.