Fibroblast growth factor signaling in liver carcinogenesis Fibroblast growth factor signalling: from development to cancer. The FGF19/FGFR4 pathway with its main components and targets of inhibitory agents. Fibroblast growth factors, or FGFs, are a large family of polypeptide cytokines exhibiting a pleiotropy of functions, from cell growth to angiogenesis, wound healing, and tissue repair. Although current therapies target FGFRs for the treatment of Moreover, some growth factor signaling pathways such as epidermal growth factor (EGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), transforming growth factor (TGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) have also been emerged as critical players in tumorigenesis including liver The FGFR family comprises four receptor tyrosine kinases (RTKs), namely FGFR1–4. This review broadly covers the genetics and protein expression of the FGF family members and the signaling pathways involved in FGF-mediated growth regulation. Mar 1, 2014 · This website requires cookies, and the limited processing of your personal data in order to function. We found th … Fibroblast growth factor receptors (FGFRs) are a family of four receptor tyrosine kinases (FGFR1-4) that interact with both paracrine and endocrine fibroblast growth factors (FGFs). FGF15 is induced by FXR in ileal enterocytes in response to increased amounts of intestinal bile. Gene ID: 9965, updated on 8-Feb-2025. Signaling through the fibroblast growth factor (FGF) family is involved in fibrosis and its progression to cirrhosis of the liver, which is a risk factor for the development of HCC. Hepatology 59 (3), 1166–1173. fibroblast growth factor (FGF), fibroblast growth factor receptor (FGFR), β-Klotho (KLB), farnesoid x receptor (FXR), cytochrome P450 7A1 (CYP7A1), bile salt efflux pump (BSEP), small heterodimeric partner (SHP), liver receptor homolog 1 (LRH-1), hepatocyte nuclear factor 4 alpha (HNF4), FGFR substrate 2 alpha (FRS2α), solute transporter alpha Abnormal activation of wild-type Notch signaling and its role in carcinogenesis and progression can be observed in HCC 413 and other aggressive tumors. Moreover, CAFs secrete cytokines and other factors which may promote tumor growth, tumor angiogenesis, and epithelial to mesenchymal transition (EMT). Oct 1, 2015 · Fibrosis is a highly conserved and coordinated protective response to tissue injury. Scientists have relentlessly pursued the intricacies of carcinogenesis and explored ways to prevent and treat cancer. Bile acid signaling of FGF19-FGFR4 in the liver. for fibroblast growth factor signaling in embryonic Apr 15, 2021 · Fibroblast growth factor signaling in liver carcinogenesis. Recent studies demonstrated that miR-214 could inhibit liver cancer cell invasion through downregulation of FGFR1 expression ( 44 ). 417–419 Notch signaling is overactivated in human HCC and mouse HCC models, downregulation of SULF2-mediated cell growth was associated with increased binding of fibroblast growth factor 2 (FGF2), phosphorylation of extracellular signal-regulated kinase and AKT, and expression of GPC3. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes including embryonic development cell growth, morphogenesis, tissue repair, tumor growth and invasion. Knockdown of GPC3 attenuated FGF2 binding in SULF2-expressing HCC cells. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy. Furthermore, several alterations in FGF/FGF receptor (FGFR) signaling correlate with the outcomes of HCC patients, suggesting that signaling through this family of Mar 17, 2021 · The family of fibroblast growth factor (FGF) and its receptors (FGFR) are involved in various biological processes, including embryogenesis, morphogenesis, wound repair, and cell growth. This interaction activates the phosphorylation of tyrosine kinase residues, thereby triggering downstream signaling pathways, including RAS-MAPK, JAK-STAT, PI3K Feb 25, 2019 · The external factors that modulate Hippo signaling remain elusive. These receptors are distributed across various tissues and organs in the body, facilitating numerous cells signaling pathways by interacting with FGF ligands to regulate processes such as cell growth, differentiation, and metabolic functions (Seitz & Hellerbrand, 2021). Several CAF-dependent mechanisms support tumor growth in the liver . The fibroblast growth factor receptor (FGFR) pathway is increasingly acknowledged to play a role in the pathogenesis of hepatocellular carcinoma (HCC) and is postulated to be upregulated as a mechanism of resistance to anti-VEGF treatment. The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. 1002/hep. Multikinase inhibitors targeting FGF signaling are currently under investigation in clinical trials. Aug 2, 2018 · Fibroblast growth factor receptors (FGFR) play a significant role in both embryonic development and in adults. 26679 PubMed Abstract | CrossRef Full Text | Google Scholar Sandhu DS, Baichoo E, Roberts LR. This interaction activates the phosphorylation of tyrosine kinase residues, thereby triggering downstream signaling pathways, including RAS-MAPK, JAK-STAT, PI3K-AKT Apr 1, 2012 · In this review, the evidence for a role of fibroblast growth factor receptor (FGFR) mediated signalling in carcinogenesis are considered and relevant underlying mechanisms highlighted. Fibroblast growth factor receptors (FGFRs) are a family of four receptor tyrosine kinases (FGFR1–4) that interact with both paracrine and endocrine fibroblast growth factors (FGFs). For example, CAFs can change the ECM stiffness and in turn affect tumorigenesis. Carcinogenesis is a complex, multi-faceted, and multi-stage process, with numerous underlying causes, including inflammation and fibrosis. Consistently, downregulation of miR-214 and overexpression of FGFR1 were observed in HCC samples. Subsequent studies have shown that FGF-19 and its mouse ortholog, FGF-15, also function in adult animals. This May 29, 2014 · Several alterations in FGF signaling correlate with poor outcome in HCC patients, suggesting that this family of signaling molecules plays an important role in the development of HCC. FGF signalling mediated by FGFR follows a classic receptor tyrosine kinase signalling pathway and its deregulation at various points of its cascade could result Mar 11, 2020 · Fibroblast growth factor (FGF) signaling plays an important role in the regulation of many biological Several alterations in FGF-signaling have been found to affect liver carcinogenesis 7. Hepatology 2014;59:1166-73. Nat Rev Cancer 2010;10:116-29. Exploring mechanisms of FGF signalling through the lens of structural biology. Here, we report that FGF15 activates Hippo signaling to suppress bile acid metabolism, liver overgrowth, and tumorigenesis. We emphasize the role of FGFs in the pathogenesis of hepatocellular carcinoma (HCC), including their effects on regulation of the tumor microenvironment and angiogenesis. Fibroblast growth factors (FGFs) and their receptors (FGFRs) are important regulators of wound healing and repair as initially demonstrated for the skin. FGF, fibroblast growth factor; HCC, hepatocellular carcinoma. Summary. FGF19 plays a syngeneic function with other signaling pathways in primary liver cancer development, such as epidermal growth factor receptor, Wnt/β-catenin, the endoplasmic reticulum–related signaling pathway, STAT3/IL-6, RAS, and extracellular signal–regulated protein kinase, among others. The aberrant FGF/FGFR signaling is also observed in multiple cancers, including HCC. Upon binding with ligands, FGFR signaling is activated and triggers various downstream signal cascades that are implicated in diverse biological processes. Also liver fibrosis is a wound healing process in response to chronic liver injury. 3. Jan 13, 2025 · In contemporary times, cancer poses the most significant threat to human life and safety. doi:10. Apr 10, 2009 · Fibroblast growth factor-19 (FGF-19) was originally identified as a signal promoting the development of the inner ear in chick embryos (5). Overexpression of fibroblast growth factor Hepatocellular carcinoma (HCC) is closely associated with liver fibrosis. This review broadly covers the genetics and protein expression of the FGF family members and the signaling pathways involved in FGF-mediated growth regulation. Goetz R, Mohammadi M. Mar 1, 2014 · Fibroblast growth factors, or FGFs, are a large family of polypeptide cytokines exhibiting a pleiotropy of functions, from cell growth to angiogenesis, wound healing, and tissue repair. 414–416 The oncogenic function of activated Notch signaling were more frequently found in HCC. Turner N, Grose R. The fibroblast growth factor 15/19 (FGF15/19), FGF receptor 4 (FGFR4) and beta-Klotho (KLB) correceptor signaling system, a key regulator of bile acids (BA) synthesis and intermediary metabolism, is emerging as an important player in hepatocarcinogenesis. Hepatic stellate cells (HSC) and cancer-associated myofibroblasts are key players in liver fibrogenesis and hepatocarcinogenesis. FGF19: Fibroblast Growth Factor 19, FGFR4: Fibroblast Growth Factor Receptor 4, KLB: Klotho Beta, FRS2: Fibroblast growth factor Receptor Substrate 2, GRB2: Growth factor Receptor-Bound protein 2. 4 The current review provides a detailed overview on the FGF19 signaling pathways in HCC development, including its role as a biomarker in various animal models as well as the potential clinical application of targeting FGF19 as a novel therapeutic option. Role of FGF 19-FGFR4 Pathway in Hepatocellular Carcinogenesis. Feb 1, 2010 · FGF19 was overexpressed in a subgroup of liver, of FGFs in the epithelium induces carcinogenesis through an autocrine signal loop. Cancer-associated fibroblasts (CAFs), however scientific article published on March 2014 Jul 1, 2021 · Among various well-known and newly discovered oncogenes related to HCC, fibroblast growth factor FGF) 19 is overexpressed in HCC. Fibroblast growth factor signaling in liver carcinogenesis. ipacqga nzxbl sagsfk dyayedk tzxtf ecmfl ovcesv jzdf ebac aqgz xuvu baxnk dkey uxs dxdmj
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