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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Impact Journals LLC
2016
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| Online Access: | http://psasir.upm.edu.my/id/eprint/54313/1/Fibroblast%20growth%20factor%20%20receptor%204.pdf |
| _version_ | 1796976056376229888 |
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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 | UPM |
| 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. |
| first_indexed | 2024-03-06T09:20:18Z |
| format | Article |
| id | upm.eprints-54313 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T09:20:18Z |
| publishDate | 2016 |
| publisher | Impact Journals LLC |
| record_format | dspace |
| spelling | 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 Fibroblast growth factor; Breast cancer; RNAi screen; FGFR4; FGF19 10.18632/oncotarget.9328 |
| spellingShingle | Fibroblast growth factor; Breast cancer; RNAi screen; FGFR4; FGF19 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 |
| title | 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_short | 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 |
| topic | Fibroblast growth factor; Breast cancer; RNAi screen; FGFR4; FGF19 |
| url | http://psasir.upm.edu.my/id/eprint/54313/1/Fibroblast%20growth%20factor%20%20receptor%204.pdf |
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