YAP regulates the response mechanism of RAF- and MEK-targeted therapy. (A) SGK1 protein levels were downregulated after YAP knockdown. (B) SGK1 inhibition resulted in a significant decrease in pERK1/2 (activated form) expression, while the total ERK1/2 content showed no significant difference between the two groups. (C) Cell activity measurement: SGK1i and RAF→MEK pathway inhibitor synergistic inhibition of the ERK1/2 pathway, inhibition of RKO, and HT29 cell proliferation. (D) Flow cytometry detection of apoptosis: Apoptosis induced by the RAF→MEK pathway I increased after YAP knockdown. (E,F) The RAF MEK pathway-ERK pathway participates in cell apoptosis by regulating gene expression of Bcl-2 family proteins, such as Bax Bim, and by inducing proteasomal degradation of anti-apoptotic proteins. WB detection knockdown of YAP reduces the expression level of SGK1, thereby reducing the expression of pERK, coordinating the expression of apoptosis-related factors, and increasing the apoptosis induced by the RAF→MEK pathway i. YAP, yes-associated protein; MEK, MAPK/extracellular signal-regulated kinase. *P<0.01, **P<0.05.