Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/26124204http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26124204http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

Resistance to tyrosine kinase inhibitors (TKI) of EGF receptor (EGFR) is often related to activation of other signaling pathways and evolution through a mesenchymal phenotype.

Experimental design

Because the Hedgehog (Hh) pathway has emerged as an important mediator of epithelial-to-mesenchymal transition (EMT), we studied the activation of Hh signaling in models of EGFR-TKIs intrinsic or acquired resistance from both EGFR-mutated and wild-type (WT) non-small cell lung cancer (NSCLC) cell lines.

Results

Activation of the Hh pathway was found in both models of EGFR-mutated and EGFR-WT NSCLC cell line resistant to EGFR-TKIs. In EGFR-mutated HCC827-GR cells, we found SMO (the Hh receptor) gene amplification, MET activation, and the functional interaction of these two signaling pathways. In HCC827-GR cells, inhibition of SMO or downregulation of GLI1 (the most important Hh-induced transcription factor) expression in combination with MET inhibition exerted significant antitumor activity.In EGFR-WT NSCLC cell lines resistant to EGFR inhibitors, the combined inhibition of SMO and EGFR exerted a strong antiproliferative activity with a complete inhibition of PI3K/Akt and MAPK phosphorylation. In addition, the inhibition of SMO by the use of LDE225 sensitizes EGFR-WT NSCLC cells to standard chemotherapy.

Conclusions

This result supports the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.org/dc/terms/identifier"doi:10.1158/1078-0432.ccr-14-3319"xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Martinelli E."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Fasano M."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Ciardiello F."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Santini M."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Vitagliano D."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Bianco R."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Morgillo F."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Troncone G."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Malapelle U."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Vicidomini G."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Fiorelli A."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Papaccio F."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Bellevicine C."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Accardo M."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Troiani T."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Della Corte C.M."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/author"Fabozzi A."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/name"Clin Cancer Res"xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/pages"4686-4697"xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/title"SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer."xsd:string
http://purl.uniprot.org/citations/26124204http://purl.uniprot.org/core/volume"21"xsd:string
▶