Fibroblast growth factor 19 is correlated with an unfavorable prognosis and promotes progression by activating fibroblast growth factor receptor 4 in advanced-stage serous ovarian cancer

Hu, Lingling; Cong, Lanxiang

doi:10.3892/or.2015.4212

Cited by 23 publications

(11 citation statements)

References 34 publications

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“…Tiong et al suggested that FGF19 and FGFR4 signaling mediated the viability of cancer cells through activation of the PI3K/AKT pathway in breast cancer [ 29 ]. Hu et al also suggested that patients with high expression of both FGF19 and FGFR4 had significantly poor prognoses for ovarian cancer and that FGF19 and FGFR4 signaling could promote ovarian cancer proliferation and invasion through the AKT-MAPK signaling pathway [ 30 ]. In prostate cancer, FGF19/FGFR signaling promotes cancer progression along with the presence of KLa and/or KLb as co-factors [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer

et al. 2018

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Alpha-Klotho (KLα) and beta-Klotho (KLβ) have recently been reported to correlate with cancer prognosis in some malignancies and we previously reported the association between KLα, KLβ, and urothelial carcinoma of the bladder (UCB), indicating that KLβ acts as a tumor promoter. However, the association between gamma-Klotho (KLγ) and cancer prognosis remains unclear. In the present study, we evaluated the association between KLγ and UCB. To evaluate the effect of KLγ on human bladder cancer cell lines in vitro assays were performed. Exogenous KLγ increased the ability of human bladder cancer cells to proliferate, migrate, invade, form colonies, and provide anchorage-independent growth potential. In in vivo assays, eighteen mice bearing xenografts inoculated using UM-UC-3, were randomly divided into three groups and treated with a small interfering RNA (siRNA) by intratumoral administration once a week for four weeks. Knockdown of KLγ with siRNA led to a dramatic change in tumor growth and suggested that KLγ had effects on tumor growth, including promotion of cell proliferation, inhibition of apoptosis, and enhancement of the epithelial-mesenchymal transition. To confirm the study, human tissue samples were used and patients were divided into two groups according to KLγ expression level. High expression of KLγ was significantly associated with higher stage and grade cancer and the presence of lymphovascular invasion compared to patients with lower expression of KLγ. Our results suggest that KLγ plays an important role in tumor invasion and progression and these results may lead to the development of new therapies and diagnostic methods for UCB.

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Section: Discussionmentioning

confidence: 99%

Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer

et al. 2018

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“…High expression of FGF19 predicts unfavorable prognosis of advanced-stage serous ovarian cancer (357). In vitro, FGF19 promotes ovarian cancer cell proliferation and invasion by activating the FGFR4/Akt-MAPK signaling pathway (357).…”

Section: Reproductive Tissues Cancersmentioning

confidence: 99%

Fibroblast Growth Factor 15/19: From Basic Functions to Therapeutic Perspectives

Somm

Jornayvaz

2018

Endocrine Reviews

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Discovered 20 years ago, fibroblast growth factor (FGF)19, and its mouse ortholog FGF15, were the first members of a new subfamily of FGFs able to act as hormones. During fetal life, FGF15/19 is involved in organogenesis, affecting the development of the ear, eye, heart, and brain. At adulthood, FGF15/19 is mainly produced by the ileum, acting on the liver to repress hepatic bile acid synthesis and promote postprandial nutrient partitioning. In rodents, pharmacologic doses of FGF19 induce the same antiobesity and antidiabetic actions as FGF21, with these metabolic effects being partly mediated by the brain. However, activation of hepatocyte proliferation by FGF19 has long been a challenge to its therapeutic use. Recently, genetic reengineering of the molecule has resolved this issue. Despite a global overlap in expression pattern and function, murine FGF15 and human FGF19 exhibit several differences in terms of regulation, molecular structure, signaling, and biological properties. As most of the knowledge originates from the use of FGF19 in murine models, differences between mice and humans in the biology of FGF15/19 have to be considered for a successful translation from bench to bedside. This review summarizes the basic knowledge concerning FGF15/19 in mice and humans, with a special focus on regulation of production, morphogenic properties, hepatocyte growth, bile acid homeostasis, as well as actions on glucose, lipid, and energy homeostasis. Moreover, implications and therapeutic perspectives concerning FGF19 in human diseases (including obesity, type 2 diabetes, hepatic steatosis, biliary disorders, and cancer) are also discussed.

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“…Many such alterations have involved tyrosine kinase receptors 4 , which have proven therapeutic potential in a variety of cancer types. One such tyrosine kinase receptor is FGFR4, which has been associated with prognosis in several types of cancer, including lung cancer 5 – 7 . Several molecular alterations of FGFR4 leading to different gene variants have been identified 8 .…”

Section: Introductionmentioning

confidence: 99%

The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction

Quintanal-Villalonga

Ojeda-Márquez

Marrugal

et al. 2018

Sci Rep

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The FGFR4-388Arg variant has been related to poor prognosis in several types of cancer, including lung cancer. The mechanism underlying this association has not been addressed in detail in patients with this pathology. Here, we report that this FGFR4 variant induces MAPK and STAT3 activation and causes pro-oncogenic effects in NSCLC in vitro and in vivo. This variant induces the expression of EMT-related genes, such as N-cadherin, vimentin, Snail1 and Twist1. Indeed, the induction of N-cadherin protein expression by this variant is essential for its pro-tumorigenic role. The presence of the FGFR4-388Arg variant correlates with higher N-cadherin expression levels in clinical NSCLC samples and with poorer outcome in patients with FGFR expression. These results support the prognostic role of this FGFR variant in lung cancer and show that these effects may be mediated by the induction of N-cadherin expression and an EMT phenotype.

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Fibroblast growth factor 19 is correlated with an unfavorable prognosis and promotes progression by activating fibroblast growth factor receptor 4 in advanced-stage serous ovarian cancer

Cited by 23 publications

References 34 publications

Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer

Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer

Fibroblast Growth Factor 15/19: From Basic Functions to Therapeutic Perspectives

The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction

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