Targeted BRAF Inhibition Impacts Survival in Melanoma Patients with High Levels of Wnt/β-Catenin Signaling
Figure 4
Long-term BRAFi treatment uncouples Wnt-mediated transcription from Wnt-mediated enhancement of apoptosis.
(A) A375 cells treated long-term with BRAFi or WNT3A + BRAFi were then incubated overnight with CHIR99021. Long-term BRAFi treatment does not affect the ability of CHIR99021 to activate AXIN2 transcription, but long-term WNT3A + BRAFi significantly decreases the upregulation of AXIN2 transcription by CHIR99021. (B) In cells treated with long-term BRAFi, CHIR99021 is unable to further stimulate apoptosis with BRAFi. For these experiments, bars represent the mean and standard deviation of three distinct replicates for each condition. Data were compared using one-way ANOVA with Tukey's multiple comparison post-test, and relevant comparisons are shown (***, p<0.001; *, p<0.05; n.s., not significant). Data shown are representative of two to four experiments (each with three distinct replicate plates per condition) showing the same results.