Fig. 5

PI3K/AKT and MYC pathways induce a squamous-like phenotype in EGFR-mutant LUAD models. a Western blot showing the expression of the squamous marker P40, as well as of SOX2 and EZH2 in the EGFR-mutant LUAD PDX-derived cell line Lx462 and in the PC9 cell line, expressing exogenous myrAKT, MYC, or both. b Tumor growth on subcutaneous xenografts of the control and myrAKT/MYC-overexpressing conditions for both cell lines, untreated or treated with osimertinib (N = 5 mice/condition). Mean ± SEM tumor size is shown. Representative images for H&E, TTF-1, P40 and CK5/6 IHC stains and barplot showing IHC quantification (mean ± SEM score values per group are shown) of the Lx462 (c) and PC9 (d) cell line xenografts from the subcutaneous xenografts shown in (b). e Representative images for H&E, TTF-1, P40 and CK5/6 IHC stains and barplot showing IHC quantification (mean ± SEM score values per group are shown) of the control and osimertinib-resistant Lx462 PDXs. f Bar plot showing differential phosphorylation of genes involved in the AKT pathway, as determined by an antibody array on one control and two osimertinib-resistant Lx462 PDX derivatives (OsiR-1 and OsiR-2). g Western blot assessment of the expression of MYC, P40, TTF-1, EZH2, pAKT, pPRAS40 and SOX2 in control and osimertinib-resistant Lx462 PDXs. p-values legend: *p < 0.05, **p < 0.01, ***p < 0.001