High impact information on HGF

• MDCK cells were then stimulated with scatter factor/hepatocyte growth factor (SF/HGF) to initiate invasion and tubulogenesis atop either type I collagen or interstitial stroma to determine the ability of MMPs to accelerate, modify, or disrupt morphogenic responses [1].
• Although HGF/SF secreting cells can mimic signals from Hensen's node that maintain L5 expression, they cannot rescue the ability of the node to induce anterior structures (which is normally lost after stage 4) [2].
• We therefore show that activation of the tyrosine kinase activity of HGF-R/Met via an autocrine HGF loop is directly responsible for pseudopodial protrusion, thereby explaining the motile and invasive potential of this model epithelium-derived tumor cell line [3].
• The scattering of Madin-Darby canine kidney (MDCK) epithelial cells by scatter factor/hepatocyte growth factor (SF/HGF) is associated with transcriptional induction of the urokinase gene, which occurs essentially through activation of an EBS/AP1 response element [4].
• We found that SF/HGF induces rapid and sustained phosphorylation of the extracellular signal-regulated kinase (ERK) MAPK while stimulating weakly and then repressing phosphorylation of the JUN N-terminal kinase (JNK) MAPK for several hours [4].

Biological context of HGF

• Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine that induces mitogenesis, motility, invasion, and morphogenesis of several epithelial and endothelial cell lines in culture [5].
• The met proto-oncogene is a receptor tyrosine kinase for hepatocyte growth factor/scatter factor (HGF/SF) [6].
• This sequence of events provides a model for efficient cell scattering by SF/HGF at low cell density [4].
• Despite structural similarities between MSP and HGF, the primary receptor binding site is located on the alpha chain of HGF/SF but on the beta chain of MSP [7].
• Moreover, both the HGF- and TPA-induced disruption of the cadherin-based cell-cell adhesion and the subsequent cell migration were inhibited in both sMDCK-Cdc42HsDA and -G25KDA cells [8].

Anatomical context of HGF

• The blebbing response was dependent on autocrine HGF (hepatocyte growth factor) activation of c-Met and prevented by inhibition of RhoA, ROCK and p38 MAPK (p38 mitogen-activated protein kinase), but not ERK (extracellular-signal-regulated kinase) or PI3K (phosphoinositide 3-kinase) [9].
• Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the motility of epithelial cells, initially inducing centrifugal spreading of colonies followed by disruption of cell-cell junctions and subsequent cell scattering [10].
• Conversely, expression of mutants of Vav2 that increased stress fiber formation inhibited HGF/SF-induced cell scattering [11].
• HGF/SF is a multifunctional cytokine that stimulates mitogenesis, motility, invasion, and tubulogenesis of a spectrum of epithelial and endothelial cells in culture [6].
• These results indicate that activation of both MAP kinase and PI 3-kinase by Ras is required for adherens junction disassembly and that this is essential for the motile response to HGF/SF [10].

Associations of HGF with chemical compounds

• The receptor for HGF/SF has been identified as the Met tyrosine kinase [5].
• The release of arachidonic acid by MDCK cells following HGF/SF stimulation is establishing this fatty acid and its metabolites as major components involved in the transduction of MET-driven signals and at the same time in the amplification of such signals [12].
• LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, inhibits HGF-induced PAK4 kinase activation, relocalisation, and cell rounding [13].
• Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived glycoprotein with a strong scattering effect on epithelial cells [14].
• Addition of ChTX (50 nM), IbTX (100 nM), Stk (100 nM) or CLT (1 microM) inhibited the HGF/SF-stimulated MDCK II cell migration [15].

Regulatory relationships of HGF

• Inhibition of JNK by HGF/SF prevents apoptosis induced by TNF-alpha [16].

Other interactions of HGF

• Macrophage-stimulating protein (MSP) and hepatocyte growth factor/scatter factor (HGF/SF) are plasminogen-related growth and motility factors that interact with cell-surface protein tyrosine kinase receptors [7].
• Membrane-associated HB-EGF modulates HGF-induced cellular responses in MDCK cells [17].
• Whereas enhancement of DNA synthesis and induction of cell flattening by SF/HGF were independent of substratum composition (i.e. occurred on both fibronectin and vitronectin surfaces), colony dispersion as a result of cell separation fails to occur or is markedly reduced on surfaces where vitronectin is the major adhesive ligand [18].
• We identified repression of JNK as a signaling target of HGF/SF for protection against TNF-alpha-induced cell death [16].

Analytical, diagnostic and therapeutic context of HGF

• HGF titration followed by a subsequent washout of the antibodies led to renewed pseudopodial protrusion and cellular movement [3].
• Immunodepletion of MAP kinase via electroporation of an anti-MAP kinase antibody, did not significantly decrease arachidonic acid release in HGF/SF-stimulated MDCK cells [12].
• Moreover, the HGF/SF protein was detected by Western blotting in the MDCK(LT)-conditioned medium [19].
• When compared with the unstimulated cells, the inhibition of cell adhesion promoted by HGF/SF correlated with an increased stability of the newly synthesized soluble E-cadherin and Pg and an altered phosphorylation pattern of E-cadherin, as determined by partial proteolytic peptide mapping [14].
• Cell migration induced by HGF/SF consisted of two distinct phases, initial cell spreading between 2 and 9 h after the start of treatment, and the scattering phase which started approximately 12 h after treatment [20].

References