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Fibroblast growth factor receptor 4 (FGF4) and fibroblast growth factor 19 (FGFR19) autocrine enhance brest cancer cells survival


Citation

Tiong, Kai Hung and Tan, Boon Shing and Choo, Heng Lungh and Chung, Felicia Fei-Lei and Hii, Ling Wei and Tan, Si Hoey and Khor, Nelson Tze Woei and Wong, Shew Fung and See, Sze Jia and Tan, Yuen Fen and Rosli, Rozita and Cheong, Soon Keng and Leong, Chee Onn (2016) Fibroblast growth factor receptor 4 (FGF4) and fibroblast growth factor 19 (FGFR19) autocrine enhance brest cancer cells survival. Oncotarget, 7 (36). pp. 57633-57650. ISSN 1949-2553

Abstract

Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.


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Official URL or Download Paper: http://europepmc.org/abstract/pmc/pmc5295378

Additional Metadata

Item Type: Article
Subject: Fibroblast growth factor; Breast cancer; RNAi screen; FGFR4; FGF19
Divisions: Institute of Bioscience
DOI Number: https://doi.org/10.18632/oncotarget.9328
Publisher: Impact Journals LLC
Depositing User: Nurul Ainie Mokhtar
Date Deposited: 13 Mar 2018 04:04
Last Modified: 13 Mar 2018 04:04
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.18632/oncotarget.9328
URI: http://psasir.upm.edu.my/id/eprint/54313
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