Abstract
Increasing evidence points to a key role played by epithelial-mesenchymal transition (EMT) in cancer progression and drug resistance. In this study, we used wet and in silico approaches to investigate whether EMT phenotypes are associated to resistance to target therapy in a non-small cell lung cancer model system harboring activating mutations of the epidermal growth factor receptor. The combination of different analysis techniques allowed us to describe intermediate/hybrid and complete EMT phenotypes respectively in HCC827- and HCC4006-derived drug-resistant human cancer cell lines. Interestingly, intermediate/hybrid EMT phenotypes, a collective cell migration and increased stem-like ability associate to resistance to the epidermal growth factor receptor inhibitor, erlotinib, in HCC827 derived cell lines. Moreover, the use of three complementary approaches for gene expression analysis supported the identification of a small EMT-related gene list, which may have otherwise been overlooked by standard stand-alone methods for gene expression analysis.
Highlights
Epithelial-mesenchymal transition (EMT) - wherein epithelial cells depolarize, lose their cell–cell contacts and gain an elongated fibroblast-like or amoeboid shape - plays important roles in embryonic development, tissue repair and cancer biology [1,2,3]
Increasing evidence points to a key role played by epithelial-mesenchymal transition (EMT) in cancer progression and drug resistance
In order to investigate mechanisms leading to resistance to epidermal growth factor receptor (EGFR)-targeted therapy, two nonsmall cell lung cancer (NSCLC) cell lines (HCC827 and HCC4006) have been used to derive in vitro models of acquired resistance to the EGFR tyrosine kinase inhibitor (TKI) erlotinib [30]
Summary
Epithelial-mesenchymal transition (EMT) - wherein epithelial cells depolarize, lose their cell–cell contacts and gain an elongated fibroblast-like or amoeboid shape - plays important roles in embryonic development, tissue repair and cancer biology [1,2,3]. Mostly in vitro, have supported the hypothesis that during cancer progression tumor cells undergo dynamic and reversible transitions from epithelial to mesenchymal, and from mesenchymal to epithelial (MET) phenotypes and that. The EMT/MET hypothesis as a driving force for cancer invasion and metastasis has been recently challenged by very elegant in vivo murine studies [7, 8]. In these studies, EMT was not rate limiting for invasion and metastasis, but rather associated to chemotherapy resistance [7, 8]. Circulating tumor cell (CTC) clusters have been increasingly observed in the bloodstream of many patients with aggressive malignancies including lung cancer and these clusters have been associated with worse clinical outcomes as compared to the presence of single CTCs [17,18,19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
