Cover Image

Fibroblast growth factor receptor 4 (FGF4) and fibroblast growth factor 19 (FGFR19) autocrine enhance brest 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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Impact Journals LLC 2016
Online Access:http://psasir.upm.edu.my/id/eprint/54313/1/Fibroblast%20growth%20factor%20%20receptor%204.pdf
http://psasir.upm.edu.my/id/eprint/54313/
http://europepmc.org/abstract/pmc/pmc5295378
Tags: Add Tag
No Tags, Be the first to tag this record!
id my.upm.eprints.54313
record_format eprints
spelling my.upm.eprints.543132018-03-13T04:04:44Z http://psasir.upm.edu.my/id/eprint/54313/ Fibroblast growth factor receptor 4 (FGF4) and fibroblast growth factor 19 (FGFR19) autocrine enhance brest 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 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 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/54313/1/Fibroblast%20growth%20factor%20%20receptor%204.pdf 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 http://europepmc.org/abstract/pmc/pmc5295378 10.18632/oncotarget.9328
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
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.
format Article
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
spellingShingle 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 (FGF4) and fibroblast growth factor 19 (FGFR19) autocrine enhance brest cancer cells survival
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
title Fibroblast growth factor receptor 4 (FGF4) and fibroblast growth factor 19 (FGFR19) autocrine enhance brest cancer cells survival
title_short Fibroblast growth factor receptor 4 (FGF4) and fibroblast growth factor 19 (FGFR19) autocrine enhance brest cancer cells survival
title_full Fibroblast growth factor receptor 4 (FGF4) and fibroblast growth factor 19 (FGFR19) autocrine enhance brest cancer cells survival
title_fullStr Fibroblast growth factor receptor 4 (FGF4) and fibroblast growth factor 19 (FGFR19) autocrine enhance brest cancer cells survival
title_full_unstemmed Fibroblast growth factor receptor 4 (FGF4) and fibroblast growth factor 19 (FGFR19) autocrine enhance brest cancer cells survival
title_sort fibroblast growth factor receptor 4 (fgf4) and fibroblast growth factor 19 (fgfr19) autocrine enhance brest cancer cells survival
publisher Impact Journals LLC
publishDate 2016
url http://psasir.upm.edu.my/id/eprint/54313/1/Fibroblast%20growth%20factor%20%20receptor%204.pdf
http://psasir.upm.edu.my/id/eprint/54313/
http://europepmc.org/abstract/pmc/pmc5295378
_version_ 1643835612462055424
score 13.211869

Similar Items