Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor

Montesano, Roberto; Matsumoto, Kunio; Nakamura, Toshikazu; Orci, Lelio

doi:10.1016/0092-8674(91)90363-4

Cited by 1,120 publications

(652 citation statements)

References 37 publications

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“…HGF/SF is a cytokine with unique properties (exerting multiple functions), such as mitogenic and motogenic effects on a variety of normal and transformed cells, and angiogenic (Bussolino et al, 1992;Grant et al, 1993) and morphogenic activity (Montesano et al, 1991). These diverse activities are mediated via a single receptor encoded by the c-MET protooncogene (Naldini et al, 1991;Weidner et al, 1993) al., 1986).…”

Section: Discussionmentioning

confidence: 99%

Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas

Olivero¹,

et al. 1996

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Summary Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the invasive growth of epithelial cells via the c-MET oncogene-encoded receptor. In normal lung, both the receptor and the ligand are detected, and the latter is known to be a mitogenic and a motogenic factor for both cultured bronchial epithelial cells and non-small-cell carcinoma lines. Here, ligand and receptor expression was examined in 42 samples of primary human non-small-cell lung carcinoma of different histotype. Each carcinoma sample was compared with adjacent normal lung tissue. The MetlHGF receptor was found to be 2 to 10-fold increased in 25% of carcinoma samples (P=0.0113). The ligand, HGF/SF, was found to be 10 to 100-fold overexpressed in carcinoma samples (P<0.0001). Notably, while HGF/SF was occasionally detectable and found exclusively as a single-chain inactive precursor in normal tissues, it was constantly in the biologically-active heterodimeric form in carcinomas. Immunohistochemical staining showed homogeneous expression of both the receptor and the ligand in carcinoma samples, whereas staining was barely detectable in their normal counterparts. These data show that HGF/SF is overexpressed and consistently activated in non-small-cell lung carcinomas and may contribute to the invasive growth of lung cancer.

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Section: Discussionmentioning

confidence: 99%

Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas

Olivero¹,

et al. 1996

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“…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). MET function is required for various morphogenetic events in both embryonic and adult life 21,22 and it drives the malignant progression of several different types of tumours 23 .…”

Section: Introductionmentioning

confidence: 99%

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

Trusolino

Bertotti

Comoglio

2010

Nat Rev Mol Cell Biol

1,083

1,076

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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). ...

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“…MET is the high-affinity receptor for hepatocyte growth factor (HGF, also known as scatter factor; Bottaro et al, 1991), a secreted protein independently identified as both a fibroblast motility factor (Stoker et al, 1987;Montesano et al, 1991) and a mitogenic stimulator of hepatocytes (Nakamura et al, 1989;Zarnegar and Michalopoulos, 1989). Structurally, MET is a disulfide-linked heterodimer with an extracellular ␣ chain and a large ␤ chain that spans the cell membrane and contains both the tyrosine kinase domain and a conserved C-terminal multi-substrate docking site (Y 1349 VHVNATY 1356 VNV).…”

Section: Introductionmentioning

confidence: 99%

hgf/c‐met expression and functional analysis during zebrafish embryogenesis

Latimer

Jessen

2008

Developmental Dynamics

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Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor

Cited by 1,120 publications

References 37 publications

Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas

Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas

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

hgf/c‐met expression and functional analysis during zebrafish embryogenesis

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