Research Papers:

Characterization of epithelial-mesenchymal transition intermediate/hybrid phenotypes associated to resistance to EGFR inhibitors in non-small cell lung cancer cell lines

Valentina Fustaino, Dario Presutti, Teresa Colombo, Beatrice Cardinali, Giuliana Papoff, Rossella Brandi, Paola Bertolazzi, Giovanni Felici and Giovina Ruberti _

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Oncotarget. 2017; 8:103340-103363. https://doi.org/10.18632/oncotarget.21132

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Valentina Fustaino1,2,*, Dario Presutti1,*, Teresa Colombo2, Beatrice Cardinali1, Giuliana Papoff1, Rossella Brandi3, Paola Bertolazzi4,2, Giovanni Felici2,** and Giovina Ruberti1,**

1Institute of Cell Biology and Neurobiology, National Research Council (IBCN-CNR), Monterotondo, Rome, Italy

2Institute for Systems Analysis and Computer Science “Antonio Ruberti” National Research Council, (IASI-CNR), Rome, Italy

3Genomics facility of the European Brain Research Institute, “Rita Levi-Montalcini” (EBRI), Rome, Italy

4SYSBIO Center for Systems Biology, Milan, Italy

*These authors have contributed equally to this work

**Senior authors have contributed equally to this work

Correspondence to:

Giovina Ruberti, email: [email protected]

Giovanni Felici, email: [email protected]

Keywords: EMT intermediate/hybrid phenotype, NSCLC, EGFR, erlotinib, microarray data

Received: October 04, 2016     Accepted: August 23, 2017     Published: September 22, 2017


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.

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