HMGB1 (high-mobility group box 1) protein, a pleiotropic cytokine released by several cell types under physiological and pathological conditions, has been identified as a signal molecule active on A431 cells. Although extracellular HMGB1 itself does not trigger any detectable signalling effect on these cells, it induces an increased susceptibility to EGF (epidermal growth factor) stimulation. Specifically, at concentrations of EGF which promote undetectable or limited cell responses, the addition of sub-nanomolar concentrations of HMGB1 potentiates the effect of EGF by specifically activating a downstream pathway that leads to enhanced cell motility through an increase in Ca2+ influx, activation of extracellular-signal-regulated kinase 1/2 and remodelling of the actin cytoskeleton. These results, which identify extracellular HMGB1 as an activator of human tumour cell migration operating in concert with EGF, have important implications in the search for novel strategies to control tumour progression and metastatic invasion.
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July 2005
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Research Article|
June 21 2005
Activation of A431 human carcinoma cell motility by extracellular high-mobility group box 1 protein and epidermal growth factor stimuli
Bianca SPARATORE;
Bianca SPARATORE
1
*Department of Experimental Medicine, Biochemistry Section and Centre of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, 1-16132 Genoa, Italy
1To whom correspondence should be addressed (email traspar@unige.it).
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Mauro PATRONE;
Mauro PATRONE
†Department of Environmental and Life Sciences, University of Eastern Piedmont “Amedeo Avogadro”, Via Bellini 25/G, 15100 Alessandria, Italy
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Mario PASSALACQUA;
Mario PASSALACQUA
*Department of Experimental Medicine, Biochemistry Section and Centre of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, 1-16132 Genoa, Italy
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Marco PEDRAZZI;
Marco PEDRAZZI
*Department of Experimental Medicine, Biochemistry Section and Centre of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, 1-16132 Genoa, Italy
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Sabina LEDDA;
Sabina LEDDA
*Department of Experimental Medicine, Biochemistry Section and Centre of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, 1-16132 Genoa, Italy
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Sandro PONTREMOLI;
Sandro PONTREMOLI
*Department of Experimental Medicine, Biochemistry Section and Centre of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, 1-16132 Genoa, Italy
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Edon MELLONI
Edon MELLONI
*Department of Experimental Medicine, Biochemistry Section and Centre of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, 1-16132 Genoa, Italy
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Publisher: Portland Press Ltd
Received:
January 06 2005
Revision Received:
February 21 2005
Accepted:
February 28 2005
Accepted Manuscript online:
February 28 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 389 (1): 215–221.
Article history
Received:
January 06 2005
Revision Received:
February 21 2005
Accepted:
February 28 2005
Accepted Manuscript online:
February 28 2005
Citation
Bianca SPARATORE, Mauro PATRONE, Mario PASSALACQUA, Marco PEDRAZZI, Sabina LEDDA, Sandro PONTREMOLI, Edon MELLONI; Activation of A431 human carcinoma cell motility by extracellular high-mobility group box 1 protein and epidermal growth factor stimuli. Biochem J 1 July 2005; 389 (1): 215–221. doi: https://doi.org/10.1042/BJ20050053
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