Characterization of an EMT intermediate phenotype associated to resistance to EGFR inhibitors in non small cell lung cancer cell lines

Epithelial-mesenchymal transition (EMT) plays a critical role in development and adult tissue homeostasis as well as in cancer progression. Lung cancer is the leading cause of cancer related deaths worldwide with non-small cell lung cancer (NSCLC) being the predominant form of the disease. Approximately 10-30% of NSCLC patients have activating mutations in the epidermal growth factor receptor (EGFR) gene. Targeting EGFR in these patients has shown initial and significant success in the clinic although acquired resistance invariably develops. Increasing evidence points to a key role played by EMT in cancer progression and drug resistance. In this study, we used wet and in silico approaches to investigate whether the EMT phenotype was associated to Erlotinib (ERL)-resistance in a NSCLC cellular model system. The combination of different analysis techniques allowed us to describe intermediate and complete EMT phenotypes respectively in HCC827- and HCC4006-derived ERL-resistant cell lines. Interestingly, EMT intermediate phenotypes and collective cell migration features associated to resistance to target therapy in all ERL-resistant HCC827 derived cell lines. Moreover, the use of three complementary approaches for gene expression analysis supported the identification of a small interesting EMT-related gene list, which should be otherwise overlooked by standard stand-alone methods for gene expression analysis.