Publication: The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction.
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Identifiers
Date
2018-02-05
Authors
Quintanal-Villalonga, Álvaro
Ojeda-Márquez, Laura
Marrugal, Ángela
Yagüe, Patricia
Ponce-Aix, Santiago
Salinas, Ana
Carnero, Amancio
Ferrer, Irene
Molina-Pinelo, Sonia
Paz-Ares, Luis
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
The FGFR4-388Arg variant has been related to poor prognosis in several types of cancer, including lung cancer. The mechanism underlying this association has not been addressed in detail in patients with this pathology. Here, we report that this FGFR4 variant induces MAPK and STAT3 activation and causes pro-oncogenic effects in NSCLC in vitro and in vivo. This variant induces the expression of EMT-related genes, such as N-cadherin, vimentin, Snail1 and Twist1. Indeed, the induction of N-cadherin protein expression by this variant is essential for its pro-tumorigenic role. The presence of the FGFR4-388Arg variant correlates with higher N-cadherin expression levels in clinical NSCLC samples and with poorer outcome in patients with FGFR expression. These results support the prognostic role of this FGFR variant in lung cancer and show that these effects may be mediated by the induction of N-cadherin expression and an EMT phenotype.
Description
MeSH Terms
Animals
Antigens, CD
Cadherins
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Disease Progression
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
Heterografts
Humans
Lung Neoplasms
Male
Mice
Mice, Nude
Mitogen-Activated Protein Kinases
Mutation
Nuclear Proteins
Prognosis
Receptor, Fibroblast Growth Factor, Type 4
STAT3 Transcription Factor
Snail Family Transcription Factors
Survival Analysis
Twist-Related Protein 1
Vimentin
Antigens, CD
Cadherins
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Disease Progression
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
Heterografts
Humans
Lung Neoplasms
Male
Mice
Mice, Nude
Mitogen-Activated Protein Kinases
Mutation
Nuclear Proteins
Prognosis
Receptor, Fibroblast Growth Factor, Type 4
STAT3 Transcription Factor
Snail Family Transcription Factors
Survival Analysis
Twist-Related Protein 1
Vimentin