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Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival

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 ident...

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Autores principales: Tiong, Kai Hung, Tan, Boon Shing, Choo, Heng Lungh, Chung, Felicia Fei-Lei, Hii, Ling-Wei, Tan, Si Hoey, Khor, Nelson Tze Woei, Wong, Shew Fung, See, Sze-Jia, Tan, Yuen-Fen, Rosli, Rozita, Cheong, Soon-Keng, Leong, Chee-Onn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295378/
https://www.ncbi.nlm.nih.gov/pubmed/27192118
http://dx.doi.org/10.18632/oncotarget.9328
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author Tiong, Kai Hung
Tan, Boon Shing
Choo, Heng Lungh
Chung, Felicia Fei-Lei
Hii, Ling-Wei
Tan, Si Hoey
Khor, Nelson Tze Woei
Wong, Shew Fung
See, Sze-Jia
Tan, Yuen-Fen
Rosli, Rozita
Cheong, Soon-Keng
Leong, Chee-Onn
author_facet Tiong, Kai Hung
Tan, Boon Shing
Choo, Heng Lungh
Chung, Felicia Fei-Lei
Hii, Ling-Wei
Tan, Si Hoey
Khor, Nelson Tze Woei
Wong, Shew Fung
See, Sze-Jia
Tan, Yuen-Fen
Rosli, Rozita
Cheong, Soon-Keng
Leong, Chee-Onn
author_sort Tiong, Kai Hung
collection PubMed
description 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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spelling pubmed-52953782017-02-08 Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival Tiong, Kai Hung Tan, Boon Shing Choo, Heng Lungh Chung, Felicia Fei-Lei Hii, Ling-Wei Tan, Si Hoey Khor, Nelson Tze Woei Wong, Shew Fung See, Sze-Jia Tan, Yuen-Fen Rosli, Rozita Cheong, Soon-Keng Leong, Chee-Onn Oncotarget Research Paper 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. Impact Journals LLC 2016-05-12 /pmc/articles/PMC5295378/ /pubmed/27192118 http://dx.doi.org/10.18632/oncotarget.9328 Text en Copyright: © 2016 Tiong et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Tiong, Kai Hung
Tan, Boon Shing
Choo, Heng Lungh
Chung, Felicia Fei-Lei
Hii, Ling-Wei
Tan, Si Hoey
Khor, Nelson Tze Woei
Wong, Shew Fung
See, Sze-Jia
Tan, Yuen-Fen
Rosli, Rozita
Cheong, Soon-Keng
Leong, Chee-Onn
Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival
title Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival
title_full Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival
title_fullStr Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival
title_full_unstemmed Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival
title_short Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival
title_sort fibroblast growth factor receptor 4 (fgfr4) and fibroblast growth factor 19 (fgf19) autocrine enhance breast cancer cells survival
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295378/
https://www.ncbi.nlm.nih.gov/pubmed/27192118
http://dx.doi.org/10.18632/oncotarget.9328
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