fig5

Figure 5. TGFβ/Smad, but not the PI3K-AKT pathway, mediates activation of the Wnt/β-catenin pathway through GSK3β Ser9 phosphorylation in 60400 and 70301 cells treated with the CDK4/6 inhibitor PD-0332991 for 72 h. (A) PD-0332991 treatment did not increase p-AKT (Ser473) levels in pancreatic cancer cells; (B) Inhibition of the PI3K-AKT pathway at the PI3Kα/δ node with GDC0941 failed to reverse EMT or suppress Wnt/β-catenin signaling, but instead enhanced EMT; (C) Inhibition of the PI3K-AKT pathway at the AKT node with MK2206 also failed to reverse EMT or suppress Wnt/β-catenin signaling, while also promoting EMT; (D) PD-0332991 activated the TGFβ/Smad pathway by upregulating pSmad3 in pancreatic cancer cells; (E and F) Inhibition of the TGFβ/Smad pathway with the small molecule inhibitors LY364947 or LY2109761 suppressed EMT and Wnt/β-catenin signaling. CDK4/6: Cyclin-dependent kinases 4 and 6; EMT: epithelial-to-mesenchymal transition.