NDLI: Gefitinib Inhibits Invasive Phenotype and Epithelial-Mesenchymal Transition in Drug-Resistant NSCLC Cells with MET Amplification

Content Provider	PubMed Central
Author	Monica, Silvia La Caffarra, Cristina Saccani, Francesca Galvani, Elena Galetti, Maricla Claudia, Fumarola Bonelli, Mara Cavazzoni, Andrea Cretella, Daniele Rita, Sirangelo Gatti, Rita Marcello, Tiseo Ardizzoni, Andrea Giovannetti, Elisa Giorgio, Petronini Pier Alfieri, Roberta R.
Editor	Lee, Jung Weon
Copyright Year	2013
Abstract	Despite the initial response, all patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). The EGFR-T790M secondary mutation is responsible for half of acquired resistance cases, while MET amplification has been associated with acquired resistance in about 5-15% of NSCLCs. Clinical findings indicate the retained addiction of resistant tumors on EGFR signaling. Therefore, we evaluated the molecular mechanisms supporting the therapeutic potential of gefitinib maintenance in the HCC827 GR5 NSCLC cell line harbouring MET amplification as acquired resistance mechanism. We demonstrated that resistant cells can proliferate and survive regardless of the presence of gefitinib, whereas the absence of the drug significantly enhanced cell migration and invasion. Moreover, the continuous exposure to gefitinib prevented the epithelial-mesenchymal transition (EMT) with increased E-cadherin expression and down-regulation of vimentin and N-cadherin. Importantly, the inhibition of cellular migration was correlated with the suppression of EGFR-dependent Src, STAT5 and p38 signaling as assessed by a specific kinase array, western blot analysis and silencing functional studies. On the contrary, the lack of effect of gefitinib on EGFR phosphorylation in the H1975 cells (EGFR-T790M) correlated with the absence of effects on cell migration and invasion. In conclusion, our findings suggest that certain EGFR-mutated patients may still benefit from a second-line therapy including gefitinib based on the specific mechanism underlying tumor cell resistance.
Related Links	http://dx.doi.org/10.1371/journal.pone.0078656
Starting Page	78656
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	10
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-10-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

MET Gene Amplification and MET Receptor Activation Are Not Sufficient to Predict Efficacy of Combined MET and EGFR Inhibitors in EGFR TKI-Resistant NSCLC Cells

Collagen XV Inhibits Epithelial to Mesenchymal Transition in Pancreatic Adenocarcinoma Cells

Sorafenib Inhibits Epithelial-Mesenchymal Transition through an Epigenetic-Based Mechanism in Human Lung Epithelial Cells

Triclosan Potentiates Epithelial-To-Mesenchymal Transition in Anoikis-Resistant Human Lung Cancer Cells

Suppression of TGFβ-Induced Epithelial-Mesenchymal Transition Like Phenotype by a PIAS1 Regulated Sumoylation Pathway in NMuMG Epithelial Cells

Progesterone Inhibits Epithelial-to-Mesenchymal Transition in Endometrial Cancer

Eosinophils Promote Epithelial to Mesenchymal Transition of Bronchial Epithelial Cells

MicroRNA-147 Induces a Mesenchymal-To-Epithelial Transition (MET) and Reverses EGFR Inhibitor Resistance

Protons Sensitize Epithelial Cells to Mesenchymal Transition

Gefitinib Inhibits Invasive Phenotype and Epithelial-Mesenchymal Transition in Drug-Resistant NSCLC Cells with MET Amplification

Similar Documents

MET Gene Amplification and MET Receptor Activation Are Not Sufficient to Predict Efficacy of Combined MET and EGFR Inhibitors in EGFR TKI-Resistant NSCLC Cells

Collagen XV Inhibits Epithelial to Mesenchymal Transition in Pancreatic Adenocarcinoma Cells

Sorafenib Inhibits Epithelial-Mesenchymal Transition through an Epigenetic-Based Mechanism in Human Lung Epithelial Cells

Triclosan Potentiates Epithelial-To-Mesenchymal Transition in Anoikis-Resistant Human Lung Cancer Cells

Suppression of TGFβ-Induced Epithelial-Mesenchymal Transition Like Phenotype by a PIAS1 Regulated Sumoylation Pathway in NMuMG Epithelial Cells

Progesterone Inhibits Epithelial-to-Mesenchymal Transition in Endometrial Cancer

Eosinophils Promote Epithelial to Mesenchymal Transition of Bronchial Epithelial Cells

MicroRNA-147 Induces a Mesenchymal-To-Epithelial Transition (MET) and Reverses EGFR Inhibitor Resistance

Protons Sensitize Epithelial Cells to Mesenchymal Transition

Gefitinib Inhibits Invasive Phenotype and Epithelial-Mesenchymal Transition in Drug-Resistant NSCLC Cells with MET Amplification