Please use this identifier to cite or link to this item:
|Title:||Fibroblast growth factor receptor 4 regulates proliferation, anti-apoptosis and alpha-fetoprotein secretion during hepatocellular carcinoma progression and represents a potential target for therapeutic intervention||Authors:||Ho, H.K.
|Issue Date:||Jan-2009||Citation:||Ho, H.K., Pok, S., Streit, S., Ruhe, J.E., Hart, S., Lim, K.S., Loo, H.L., Aung, M.O., Lim, S.G., Ullrich, A. (2009-01). Fibroblast growth factor receptor 4 regulates proliferation, anti-apoptosis and alpha-fetoprotein secretion during hepatocellular carcinoma progression and represents a potential target for therapeutic intervention. Journal of Hepatology 50 (1) : 118-127. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jhep.2008.08.015||Abstract:||Background/Aims: FGFR4, a member of the fibroblast growth factor receptor family, has been recently associated with progression of melanoma, breast and head and neck carcinoma. Given its uniquely high expression in the liver, we investigated its contributory role to hepatocellular carcinoma (HCC). Methods: We performed a comprehensive sequencing of full-length FGFR4 transcript in 57 tumor/normal HCC tissue pairs, and quantified their mRNA expressions. Notable mutations and expression patterns were correlated with patient data. Clinically significant trends were examined in in vitro models. Results: We found eight genetic alterations including two highly frequent polymorphisms (V10I and G338R). Secretion of alpha-fetoprotein (AFP), a HCC biomarker, was increased among patients bearing homozygous Arg388 alleles. One-third of these patients exhibited increased FGFR4 mRNA expression in the matched tumor/normal tissue. Subsequent in vitro perturbation of FGFR4 signaling through both FGF19-stimulation and FGFR4 silencing confirmed a mechanistic link between FGFR4 activities and tumor aggressiveness. More importantly, inhibition of FGFR activity with PD173074 exquisitely blocked HuH7 (high FGFR4 expression) proliferation as compared to control cell lines. Conclusions: FGFR4 contributes significantly to HCC progression by modulating AFP secretion, proliferation and anti-apoptosis. Its frequent overexpression in patients renders its inhibition a novel and much needed pharmacological approach against HCC. © 2008 European Association for the Study of the Liver.||Source Title:||Journal of Hepatology||URI:||http://scholarbank.nus.edu.sg/handle/10635/132791||ISSN:||01688278||DOI:||10.1016/j.jhep.2008.08.015|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Feb 25, 2021
WEB OF SCIENCETM
checked on Feb 25, 2021
checked on Feb 27, 2021
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.