Scatter factor/hepatocyte growth factor is essential for liver development

Schmidt, C; Bladt, Friedhelm; Goedecke, Stephanie Von; Brinkmann, Volker; Zschiesche, W; Sharpe, Michka; Gherardi, Ermanno; Birchmeier, Carmen

doi:10.1038/373699a0

Cited by 1,309 publications

(868 citation statements)

References 28 publications

Supporting

Mentioning

835

Contrasting

Unclassified

Order By: Relevance

“…Its ligand, hepatocyte growth factor (HGF), also known as scatter factor (SF) because of its ability to scatter cells in vitro, is produced mainly by mesenchymal cells , and consequently, interacts with the Met receptor in a paracrine or endocrine manner. Met-HGF/SF signaling is essential for many normal biological processes including embryogenesis Giancotti and Mainiero, 1994;Schmidt et al, 1995), neural induction (Streit et al, 1995), kidney development (Santos et al, 1994), tissue generation (Matsumoto and Nakamura, 1993), angiogenesis (Grant et al, 1993), and would healing (Nusrat et al, 1994). These in vivo activities are mimicked to some extent in cultured cells, where Met-HGF/SF are potent stimulators of cell growth, cell motility, and cell morphogenesis (Je ers et al, 1996c;Rosen et al, 1994).…”

Section: Resultsmentioning

confidence: 99%

Decreased fibronectin expression in Met/HGF-mediated tumorigenesis

et al. 1998

View full text Add to dashboard Cite

The tyrosine kinase receptor Met and its ligand, hepatocyte growth factor (HGF)/scatter factor are involved in the etiology and progression of a number of human cancers. Coexpression of Met and HGF in mesenchymal cells increases the tumorigenic and metastatic potential of the cells. In the studies described here, we used di erential display screening to identify changes in gene expression that are initiated by Met/HGF, and that may lead to these phenotypes. We learned that Met/ HGF signaling resulted in greatly decreased ®bronectin mRNA production in three di erent human and mouse tumor cell lines; these decreases in ®bronectin mRNA were paralleled by decreases in ®bronectin protein. We also found a progressive decrease in ®bronectin in tumor explants and metastases derived from the Met/HGF transformed cells. The absence of ®bronectin expression is a frequent cancer phenotype; our results indicate that decreases in ®bronectin correlate with, but are not essential for, MetHGF/SF-mediated tumorigenesis.

show abstract

Section: Resultsmentioning

confidence: 99%

Decreased fibronectin expression in Met/HGF-mediated tumorigenesis

et al. 1998

View full text Add to dashboard Cite

show abstract

“…During development, HGF and MET convey essential signals for the growth and survival of hepatocytes and placental trophoblast cells. In Hgf-or Met-null embryos, the liver is considerably reduced in size and the placental labyrinth is severely hypomorphic 106,107,108 (Fig. 4).…”

Section: Met Signalling In Development and Diseasementioning

confidence: 99%

“…These myogenic precursors delaminate from the dermomyotome, a structure in the dorsolateral region of somites, and travel to the limbs, tongue and diaphragm, where they differentiate to form a subset of the hypaxial muscles 109 . Ablation of the Hgf or Met genes results in complete absence of this specific muscle type, leaving all other muscle groups unaffected 104,105,106 . Finally, disruption of HGF-MET function affects the proper wiring of the nervous system, leading to reduced survival of sensory and sympathetic neurons as well as impaired outgrowth and fasciculation (axon bundling) of certain motor nerves 110,111,112 .…”

Section: Met Signalling In Development and Diseasementioning

confidence: 99%

MET signalling: principles and functions in development, organ regeneration and cancer

Trusolino

Bertotti

Comoglio

2010

Nat Rev Mol Cell Biol

1,060

1,076

View full text Add to dashboard Cite

The MET tyrosine kinase receptor (also known as the HGF receptor) promotes tissue remodelling, which underlies developmental morphogenesis, wound repair, organ homeostasis and cancer metastasis, by integrating growth, survival and migration cues in response to environmental stimuli or cell-autonomous perturbations. The versatility of MET-mediated biological responses is sustained by qualitative and quantitative signal modulation. Qualitative mechanisms include the engagement of dedicated signal transducers and the subcellular compartmentalization of MET signalling pathways, whereas quantitative regulation involves MET partnering with adaptor amplifiers or being degraded through the shedding of its extracellular domain or through intracellular ubiquitylation. Controlled activation of MET signalling can be exploited in regenerative medicine, whereas MET inhibition might slow down tumour progression.Throughout embryogenesis, cells bud off from developing tissues and move outwards to shape and pattern the complex architecture of prospective organs 1 . A similar process occurs in adult life during wound healing and tissue repair, when lingering cells migrate into injury sites to recreate the pre-existing structures 2 . The acquisition of cell motility is necessary, but not sufficient, for this event. Cells that detach from their neighbours must elude anoikis, a form of apoptotic cell death that occurs when cells lose adhesion with the extracellular matrix 3 . Moreover, migratory cells undergo extensive mitotic divisions to produce 'founder populations', which settle in newly forming organs during development or colonize worn tissues during repair 4,5 . The normal phases of embryogenesis and organ regeneration strongly resemble the pathological process of tumour invasiveness: similarly to cells at the wound edge, cells at the tumour's leading front disrupt intercellular contacts and infiltrate the adjacent surroundings, where they resist anoikis and grow before lodging in the blood vessels for systemic dissemination 6 . This resemblance is not simply a biological correlate, it has a common mechanistic basis: cancer cells resurrect the latent schemes of cellular reorganization, which are usually confined to embryonic development and damaged adult organs, and leverage them to become competent for metastasization 7 . The activities -motility, survival and proliferation -that occur in developing, injured and neoplastic tissues embody a biological programme that is defined as 'invasive growth' 8 . This is triggered by extracellular stimuli that regulate the activity of several transcription factors that, in turn, modulate the expression of a number of proteins, ranging from cytoskeletal and cell-cell junctional components to cell cycle regulators and anti-apoptotic effectors 9, 10 . One major environmental inducer of invasive growth is hepatocyte growth factor (HGF, also known as scatter factor), the ligand for the MET tyrosine kinase receptor (also known as the HGF receptor) 11,12,13,14,15,16,17,18,19,20 (Box 1). ...

show abstract

“…HGF can also stimulate motility and morphogenic changes in di erent epithelial and endothelial cell types Zarnegar and Michalopoulos, 1995), and these pleiotropic e ects play important roles during development, organogenesis and tissue regeneration. For example, HGF is essential for the normal development of both liver and placenta (Schmidt et al, 1995;Uehara et al, 1995), contributes to neural development , branching morphogenesis in various organs (Birchmeier and Gherardi, 1998), and promotes kidney and lung regeneration (Yanagita et al, 1993;Balkovetz and Lipschutz, 1999).…”

Section: Introductionmentioning

confidence: 99%