The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction

Álvaro Quintanal-Villalonga; Laura Ojeda-Márquez; Ángela Marrugal; Patricia Yagüe; Santiago Ponce-Aix; Ana Salinas; Amancio Carnero; Irene Ferrer; Sonia Molina-Pinelo; Luis Paz-Ares

doi:10.1038/s41598-018-20570-3

The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction

Álvaro Quintanal-Villalonga, Laura Ojeda-Márquez, Ángela Marrugal, Patricia Yagüe, Santiago Ponce-Aix, Ana Salinas, Amancio Carnero, Irene Ferrer, Sonia Molina-Pinelo, Luis Paz-Ares

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24 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Numéro d'article	2394
journal	Scientific Reports
Volume	8
Numéro de publication	1
Les DOIs	https://doi.org/10.1038/s41598-018-20570-3
état	Publié - 1 déc. 2018
Modification externe	Oui

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10.1038/s41598-018-20570-3

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title = "The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction",

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.",

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AU - Quintanal-Villalonga, Álvaro

AU - Ojeda-Márquez, Laura

AU - Marrugal, Ángela

AU - Yagüe, Patricia

AU - Ponce-Aix, Santiago

AU - Salinas, Ana

AU - Carnero, Amancio

AU - Ferrer, Irene

AU - Molina-Pinelo, Sonia

AU - Paz-Ares, Luis

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