Role of NF-κB signaling in hepatocyte growth factor/scatter factor-mediated cell protection

Fan, Saijun; Gao, Min; Meng, Qinghui; Laterra, John; Symons, Marc; Coniglio, Sal; Pestell, Richard G.; Goldberg, Itzhak D.; Rosen, Eliot M.

doi:10.1038/sj.onc.1208327

Cited by 106 publications

(118 citation statements)

References 64 publications

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“…However, blocking a single network node is sufficient to perturb cellular responses, indicating that the targeted inhibition of a specific signalling pathway cannot be compensated for by other, still active, regulatory tiers. This is in line with the well-established observation that obstruction of individual MET-dependent pathways adversely affects tumour growth, survival and migration in various cancer cell types and under different experimental settings 37,48,50,56,57,58,70,71,72,76,139 . For example, the integrity of JNK-and p38-dependent signals is required for MET-stimulated proliferation and anchorage-independent growth in MET-transformed fibroblasts and melanoma cells 70,71,72 , and STAT3 signalling and NF-κB activity are necessary for MET-induced onset of leiomyosarcomas and for the survival of prostate cancer cells, respectively 48,76 .…”

Section: Met Signalling In Development and Diseasesupporting

confidence: 88%

“…These inhibitors are ubiquitylated and degraded by a phosphorylation event that is triggered by the IκB kinase (IKK). In response to MET, IKK activation is mediated by the PI3K-Akt pathway and Src as signalling intermediates, but the direct distal effectors of IKK stimulation are unknown 76 . IKKinduced destruction of IκBs leads to the release of NF-κB, which translocates to the nucleus to stimulate the transcription of various genes, including mitogenic and anti-apoptotic regulators 76,77 (Fig.…”

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confidence: 99%

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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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Section: Met Signalling In Development and Diseasesupporting

confidence: 88%

mentioning

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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“…RasN17 and RasN43 reduced the basal NFkB activity to about 25-50% of control (Po0.001); and the pcDNA3 and pEXV vectors did not alter NF-kB activity. Cell transfection efficiencies were D80%, similar to the efficiency numbers found in previous transient transfection studies (Fan et al, 2001(Fan et al, , 2005.…”

Section: Stimulation Of Nf-kb Signaling By Ras Proteinssupporting

confidence: 85%

“…This pathway involves signaling through phosphatidylinositol-3-kinase (PI3K) and activation of c-Akt, a serine/threonine protein kinase (Bowers et al, 2000;Fan et al, 2000Fan et al, , 2001. The p21-associated kinase-1 (Pak1) acts downstream of c-Akt to promote cell survival; and nuclear factor-kappa B (NF-kB) and several of its target genes are downstream of these kinases in the SF-protection pathway (Fan et al, 2001(Fan et al, , 2005. In addition to these survival-promoting proteins, the multi-substrate adapter Grb2-associated binder-1 (Gab1) and the tumor suppressor phosphatase and tensin homolog (PTEN) function upstream of c-Akt to inhibit cell protection by SF (Fan et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Ras effector pathways modulate scatter factor-stimulated NF-κB signaling and protection against DNA damage

et al. 2007

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“…HGFR activation protects from apoptosis in several tumor in vitro models (Bowers et al, 2000;Fan et al, 2000Fan et al, , 2005Gao et al, 2001;Zeng et al, 2002;Derksen et al, 2003;Lal et al, 2005), and activation of b-catenin promotes the transcription of antiapoptotic genes (Dihlmann et al, 2005;Kim et al, 2005;Ma et al, 2005) and was associated with increased tumor cell survival in CRC (Ireland et al, 2004;Ougolkov et al, 2004). However, a proapoptotic role of HGF (Arakaki et al, 1998;Matteucci et al, 2003;Rasola et al, 2004) and b-catenin (Kim et al, 2000;van Gijn et al, 2001;Edlund et al, 2005) was also reported in several models.…”

Section: Discussionmentioning

confidence: 99%

A positive feedback loop between hepatocyte growth factor receptor and β-catenin sustains colorectal cancer cell invasive growth

et al. 2006

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Overexpressed or activated hepatocyte growth factor receptor, encoded by the MET proto-oncogene, was found in the majority of colorectal carcinomas (CRCs), whose stepwise progression to malignancy requires transcriptional activation of b-catenin. We here demonstrate that a functional crosstalk between Met and b-catenin signaling sustains and increases CRC cell invasive properties. Hepatocyte growth factor (HGF) stimulation prompts b-catenin tyrosine phosphorylation and dissociation from Met, and upregulates b-catenin expression via the phosphatidylinositol 3-kinase pathway in conditions that mimic those found by the invading and metastasizing cells. Additionally, a transcriptionally active form of b-catenin, known to be oncogenic, enhances Met expression. Furthermore, HGF treatment increases the activity of the b-catenin-regulated T-cell factor transcription factor in cells expressing the wild-type or the oncogenic b-catenin. In the mirror experiments, either Met or b-catenin knocking down also reduces their protein level. In biological assays, b-catenin knocking down abrogates the HGF-induced motile phenotype, whereas active b-catenin fosters ligand-independent cell scattering. Met and b-catenin also cooperate in promoting entry into the cell cycle and in protecting cells from apoptosis. In conclusion, Met and b-catenin pathways are mutually activated in CRC cells. This might generate a selfamplifying positive feedback loop resulting in the upregulation of the invasive growth properties of CRC cells.

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Role of NF-κB signaling in hepatocyte growth factor/scatter factor-mediated cell protection

Cited by 106 publications

References 64 publications

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

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

Ras effector pathways modulate scatter factor-stimulated NF-κB signaling and protection against DNA damage

A positive feedback loop between hepatocyte growth factor receptor and β-catenin sustains colorectal cancer cell invasive growth

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