20P - Context-dependent role of FGFR4 in lung tumorogenesis

Date 15 April 2016
Event ELCC 2016
Session Poster lunch
Topics Thoracic malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Álvaro Quintanal
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors Á. Quintanal1, R. Poveda1, R. Meléndez1, L. Ojeda-Márquez1, Á. Marrugal1, M.G. Velasco1, I. Ferrer1, A. Carnero2, L. Paz-Ares1, S. Molina-Pinelo1
  • 1Molecular Oncology And Novel Therapies, University Hospital 12 De Octubre, 28041 Madrid - Madrid/ES
  • 2Cancer Molecular Biology, Hospital Universitario Virgen del Rocio, 41003 Sevilla - Sevilla/ES

Abstract

Background

FGFR family of proteins has been extensively related to oncogenic properties in several types of tumors, including lung cancer. Among its members, FGFR4 has been identified as one of the most mutated genes in lung adenocarcinoma. However, its role in lung cancer has not yet been described.

Methods

mRNA from Paraffin-embedded tissue of a cohort of lung cancer patients was extracted and FGFR4 expression levels were measured and related to clinical characteristics. Lung adenocarcinoma (ADC) and squamous carcinoma (SCC) cell lines with different genetic backgrounds were transfected with plasmids to either overexpress or silence FGFR4 and several tumorigenic abilities were tested.

Results

FGFR4 mRNA is differentially expressed in ADC and SCC patients, with the latter holding the highest expression levels. Furthermore, FGFR4 increases oncogenic properties in SCC cell lines, but exerts anti-oncogenic effects in several lung ADC cell lines, suggesting a tumor suppressor role under certain circumstances. FGFR4 overexpression in ADC cell lines causes a decrease in activation of STAT3 and AKT signaling pathways. Analysis of FGFR4 mRNA expression of a cohort of lung cancer patients revealed that high FGFR4 mRNA expression was significantly associated to a shorter overall survival (OS) (p 

Conclusions

FGFR4 is able to exert pro- and anti-oncogenic effects in lung cancer cell lines, depending on the histological context. Ongoing work aims to elucidate the molecular mechanisms responsible for this differential behaviour.

Clinical trial identification

Legal entity responsible for the study

Instituto de Salud Carlos III

Funding

Instituto de Salud Carlos III

Disclosure

All authors have declared no conflicts of interest.