fig4

Figure 4. PD-0332991 promotes EMT through activation of the canonical Wnt/β-catenin pathway in PDAC cells. PD-0332991 induced EMT in a time- and dose-dependent manner by activating canonical Wnt/β-catenin signaling, with the strongest effect on N-cadherin. (A) Primary PDAC cell lines 60400 and 70301 cells treated with 1 μM PD-0332991 for 24, 48, and 72 h; (B) Dose-dependent effects of PD-0332991 (0.1-5 μM for 72 h) on 60400 and 70301 cells; (C) Direct inhibition of β-catenin with the small-molecule inhibitor MSAB suppressed PD-0332991-induced EMT and attenuated Wnt/β-catenin pathway activation; (D) Treatment with the PORCN inhibitor LGK974 altered EMT progression and Wnt/β-catenin signaling in 60400 and 70301 cells; (E and F) Inhibition of Wnt/β-catenin signaling, either by targeting PORCN or directly inhibiting β-catenin with MASB, also suppressed EMT in non-small lung cell carcinoma (A549) and glioma (U251) cells. EMT: Epithelial-to-mesenchymal transition; PDAC: pancreatic ductal adenocarcinoma.