Ask about this productRelated genes to: Fgf1 Blocking Peptide
- Gene:
- FGF1 NIH gene
- Name:
- fibroblast growth factor 1
- Previous symbol:
- FGFA
- Synonyms:
- AFGF, ECGF, ECGFA, ECGFB, HBGF1, ECGF-beta, FGF-alpha, GLIO703
- Chromosome:
- 5q31.3
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2016-10-05
Related products to: Fgf1 Blocking Peptide
Related articles to: Fgf1 Blocking Peptide
- Desmoplasia, a dense fibrotic reaction, is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and fuels chemoresistance through multiple mechanisms. Here, we evaluated heparanase (HPSE), an endoglycosidase that remodels extracellular matrix (ECM) and drives fibrogenesis, as a potential target in PDAC. Immunohistochemical analysis of human PDAC tissues showed elevated HPSE expression, along with increased levels of fibroblast growth factors 1 and 2 (FGF1/2), reflecting their liberation by HPSE-catalyzed heparan sulfate cleavage. High expression of all three proteins was associated with worse overall and disease-free survival. In vitro coculture assays showed that the HPSE inhibitor PI-88 suppressed PDAC cell-induced activation of pancreatic stellate cells (PSCs) and prevented ECM stiffening without inducing cytotoxicity. Mechanistically, tumor-derived HPSE activated ERK signaling and promoted FGF1/2 production in PSCs, both of which were effectively suppressed by PI-88. In orthotopic mouse models, gemcitabine treatment upregulated HPSE and FGF1/2, whereas gemcitabine-resistant tumors exhibited further increases in these factors, accompanied by enhanced PSC activation and collagen deposition. Importantly, triple therapy with PI-88, gemcitabine, and Abraxane significantly suppressed tumor growth and prolonged survival relative to all mono- and doublet regimens. Immune profiling revealed that this combination reduced PSC activation, contracted M2 macrophage and regulatory T cell populations, and expanded M1 macrophages, CD8⁺ T cells, and NK cells. In conclusion, these data underscore HPSE as a key driver of fibrosis and chemoresistance in PDAC and support HPSE inhibition as a promising strategy to enhance therapeutic efficacy. - Source: PubMed
Publication date: 2026/05/08
Chen Chang-JungWang Hao-ChenHuang Wen-YenChang Stanley Shi-ChungChang AlarngLin Chieh-LiangYang Chih-YaShan Yan-Shen - Cancer-induced bone pain (CIBP) is among the most common and debilitating symptoms in patients with bone metastasis. Current treatments are somewhat effective but have severe side effects. For the future development of safer CIBP treatment, in this study, we sought to investigate the mechanisms whereby the cancer/nerve interaction controls CIBP. We found that c-Kit, a receptor tyrosine kinase, was activated in the dorsal root ganglia (DRG) sensory neurons of mice with CIBP and that c-Kit's sole ligand, stem cell factor (SCF), was enhanced in the bone marrow with bone metastasis. When DRGs were treated SCF or conditioned medium from high SCF-expressing cancer cells, in vitro nerve sprouting was enhanced, and this effect was abolished with c-Kit inhibitors. Mice, intrafemorally inoculated with cancer cells that had varying SCF-expression developed CIBP and enhanced peripheral nerve sprouting in an SCF-dependent manner. Downstream proteomic analysis revealed that SCF upregulated and activated fibroblast growth factor 1 (FGF1) in DRGs. When FGF1 was knocked down in DRGs, SCF-mediated nerve sprouting was prevented. Taken together, our studies demonstrate the importance of the SCF/c-Kit axis in CIBP and nerve sprouting, and identify the SCF/c-Kit/FGF1 pathway as a potential therapeutic target for CIBP. - Source: PubMed
Publication date: 2026/05/05
Contino Kelly FOllodart JennaYu YangPark Sun HTsuzuki ShunsukeRollins KaraHeethouse Tyler MChu JoshuaSteele Laiton RKimura TakahiroLee JingyunFurdui Cristina MMiller Lance DHsu Fang-ChiShiozawa Yusuke - (1) Different classes of antidepressant drugs have been shown to activate lysophosphatidic acid (LPA) receptors, but their effects on the receptor signaling stimulated by LPA have not been fully investigated. In the present study, we examined the effect of the tricyclic antidepressant amitriptyline on the LPA-induced activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Rho signaling in C6 glioma cells and cultured rat astrocytes. (2) LPA receptor signaling was investigated by using Western blot and microscopic immunofluorescence assays. Rho activation was determined by a pull-down assay. (3) Amitriptyline potentiated the LPA-induced activation of ERK1/2 signaling, as indicated by the more than additive increases in the phosphorylation/activation of key components of this pathway including fibroblast growth factor 1 receptor, MEK1/2, ERK1/2, Elk-1, and cyclic AMP response element binding protein (CREB). Amitriptyline also enhanced the expression of brain-derived neurotrophic factor (BDNF) elicited by LPA. In contrast, the antidepressant failed to mimic the LPA-induced activation of Rho and Rho-dependent responses, such as the reversal of astrocyte stellation, accumulation of stress fibers, and the phosphorylation of focal adhesion kinase and myosin target subunit of myosin phosphatase isoform 1. Moreover, when combined with LPA, amitriptyline curtailed Rho activation and the Rho-mediated cellular responses. (4) These results demonstrate that in astroglial cells, amitriptyline exerts a balanced action on LPA-activated receptors by enhancing the neuroprotective ERK1/2-CREB-BDNF signaling and dampening the potentially detrimental Rho-ROCK pathway, and suggest that this unique property may contribute to the antidepressant activity of the drug. - Source: PubMed
Publication date: 2026/04/20
Olianas Maria CDedoni SimonaOnali Pierluigi - Galectin-3 (Gal3) is one of the most pro-inflammatory proteins and a biomarker of inflammatory diseases and cancer. Previous studies showed that Gal3 binds to αv and β1 integrins, but it is unclear how Gal3 binds to integrins. Here, we show that Gal3 bound to soluble αvβ3 and αIIbβ3 integrins in 1 mM Mn in cell-free conditions in a glycan-independent manner. Docking simulation predicts that Gal3 binds to the classical RGD-binding site (site 1) of αvβ3, but the predicted Gal3-binding site does not include galactose-binding site. RGDfV or eptifibatide inhibited Gal3 binding to αvβ3 and αIIbβ3, respectively, but lactose, a pan-galectin inhibitor, did not inhibit Gal3 binding to integrins. Point mutations of the predicted site 1 binding interface of Gal3 effectively inhibited Gal3 binding to site 1. Site 2 is involved in pro-inflammatory signaling (e.g., TNF and IL-6 secretion), and we previously showed that pro-inflammatory cytokines (e.g., CCL5 and TNF) bind to site 2 and allosteric integrin activation. Docking simulation predicted that Gal3 binds to site 2 of αvβ3 and α5β1. We found that Gal3 induced allosteric activation of soluble integrins αvβ3, αIIbβ3, and α5β1 in 1 mM Ca in cell-free conditions. Point mutations in the predicted site 2 binding interface inhibited Gal3-induced integrin activation, suggesting that Gal3 binding to site 2 is required for Gal3-induced integrin activation. Known anti-inflammatory agents, Ivermectin, NRG1, and FGF1, inhibited integrin activation induced by Gal3 in αvβ3 and αIIbβ3. These findings suggest that Gal3 binding to site 2 may be a potential mechanism of pro-inflammatory and pro-thrombotic action of Gal3. - Source: PubMed
Publication date: 2026/04/15
Takada Yoko KWan Yu-Jui YvonneTakada Yoshikazu - An important mechanism by which receptor tyrosine kinases (RTKs) mediate cellular responses involves the formation of signaling complexes through direct interactions with membrane-associated docking proteins, followed by phosphorylation of multiple tyrosine residues. These docking proteins recruit and activate downstream signaling molecules and enzymes following ligand stimulation. The docking protein FRS2α has been established as a major signaling hub activated by fibroblast growth factors (FGFs), neurotrophic factors, and other extracellular cues. Here, we show that palmitoylation of FRS2α at two sites is essential for stabilizing its myristoylation-dependent association with the plasma membrane. FGF1-induced mitogen-activated protein kinase (MAPK) activation and other cellular responses are partially restored in cells expressing FRS2α mutants deficient in either one of the two palmitoylation sites. However full restoration of signal strength including MAPK response and other FGF1-induced cellular activities requires palmitoylation at both FRS2α sites. In addition to enhancing signaling robustness, anchoring of FRS2α to the plasma membrane creates a structural platform for assembling multiprotein complexes essential for cytoskeletal reorganization associated with membrane ruffling, macropinocytosis, and other FGF1-induced processes. Finally, we demonstrate that while PC12 cells lacking FRS2α or deficient in FRS2α palmitoylation can proliferate, FGF1-induced neuronal differentiation strictly depends on the palmitoylation of the docking protein. - Source: PubMed
Publication date: 2026/04/29
An Seong JSuzuki YoshihisaMohanty JyotidarsiniTome FranciscoLax IritSchlessinger Joseph