Inhibition of LAMC2 suppressed EGFR/ERK1/2/AKT/mTOR/P70S6K cascade in PDAC. A Upregulation of EGFR transcripts in 179 PDAC samples compared to 171 non-cancerous pancreatic samples in TCGA data. B Higher expression of EGFR displayed inferior overall survival. C Pearson analysis revealed a positive correlation between LAMC2 and EFGR expression. D Epidermal growth factor (100 ng/mL) treatment induced the expression of LAMC2 in HPAC and BxPC-3 cells. E Western blotting experiments displayed robust expression of LAMC2 and EGFR in protein lysates (input) of HPAC and BxPC-3. F LAMC2 antibodies were used for immunoprecipitation in the cell lysates of HPAC and BxPC-3 and immunoprecipitated complexes were immunoblotted with EGFR antibodies. EGFR antibodies were used for immunoprecipitation and immunoprecipitated complexes were subjected to western blotting with LAMC2 antibodies. G HPAC and BxPC-3 cells (either with LAMC2 shRNA or scramble shRNA) were starved for at least 24 h followed by stimulation with EGF (100 ng/mL) for 20 min. Phosphorylation of EGFR, ERK1/2, AKT, mTOR, P70S6K, and P85S6K was demonstrated using western blotting experiments in HPAC and BxPC-3 cells. H Densitometric analysis revealed a significant decrease in phosphorylation of EGFR, ERK1/2, AKT, mTOR, P70S6K, and P85S6K