A concerted HIF-1α/MT1-MMP signalling axis regulates the expression of the 3BP2 adaptor protein in hypoxic mesenchymal stromal cells.

Increased plasticity, migratory and immunosuppressive abilities characterize mesenchymal stromal cells (MSC) which enable them to be active participants in the development of hypoxic solid tumours. Our understanding of the oncogenic adaptation of MSC to hypoxia however lacks the identification and c...

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Autores principales:	Sébastien Proulx-Bonneau, Amel Guezguez, Borhane Annabi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8bb222aef1044918ad532160a6e6b574
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spelling	oai:doaj.org-article:8bb222aef1044918ad532160a6e6b5742021-11-18T06:51:12ZA concerted HIF-1α/MT1-MMP signalling axis regulates the expression of the 3BP2 adaptor protein in hypoxic mesenchymal stromal cells.1932-620310.1371/journal.pone.0021511https://doaj.org/article/8bb222aef1044918ad532160a6e6b5742011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21738685/?tool=EBIhttps://doaj.org/toc/1932-6203Increased plasticity, migratory and immunosuppressive abilities characterize mesenchymal stromal cells (MSC) which enable them to be active participants in the development of hypoxic solid tumours. Our understanding of the oncogenic adaptation of MSC to hypoxia however lacks the identification and characterization of specific biomarkers. In this study, we assessed the hypoxic regulation of 3BP2/SH3BP2 (Abl SH3-binding protein 2), an immune response adaptor/scaffold protein which regulates leukocyte differentiation and motility. Gene silencing of 3BP2 abrogated MSC migration in response to hypoxic cues and generation of MSC stably expressing the transcription factor hypoxia inducible factor 1alpha (HIF-1α) resulted in increased endogenous 3BP2 expression as well as cell migration. Analysis of the 3BP2 promoter sequence revealed only one potential HIF-1α binding site within the human but none in the murine sequence. An alternate early signalling cascade that regulated 3BP2 expression was found to involve membrane type-1 matrix metalloproteinase (MT1-MMP) transcriptional regulation which gene silencing abrogated 3BP2 expression in response to hypoxia. Collectively, we provide evidence for a concerted HIF-1α/MT1-MMP signalling axis that explains the induction of adaptor protein 3BP2 and which may link protein binding partners together and stimulate oncogenic MSC migration. These mechanistic observations support the potential for malignant transformation of MSC within hypoxic tumour stroma and may contribute to evasion of the immune system by a tumour.Sébastien Proulx-BonneauAmel GuezguezBorhane AnnabiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 6, p e21511 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sébastien Proulx-Bonneau Amel Guezguez Borhane Annabi A concerted HIF-1α/MT1-MMP signalling axis regulates the expression of the 3BP2 adaptor protein in hypoxic mesenchymal stromal cells.
description	Increased plasticity, migratory and immunosuppressive abilities characterize mesenchymal stromal cells (MSC) which enable them to be active participants in the development of hypoxic solid tumours. Our understanding of the oncogenic adaptation of MSC to hypoxia however lacks the identification and characterization of specific biomarkers. In this study, we assessed the hypoxic regulation of 3BP2/SH3BP2 (Abl SH3-binding protein 2), an immune response adaptor/scaffold protein which regulates leukocyte differentiation and motility. Gene silencing of 3BP2 abrogated MSC migration in response to hypoxic cues and generation of MSC stably expressing the transcription factor hypoxia inducible factor 1alpha (HIF-1α) resulted in increased endogenous 3BP2 expression as well as cell migration. Analysis of the 3BP2 promoter sequence revealed only one potential HIF-1α binding site within the human but none in the murine sequence. An alternate early signalling cascade that regulated 3BP2 expression was found to involve membrane type-1 matrix metalloproteinase (MT1-MMP) transcriptional regulation which gene silencing abrogated 3BP2 expression in response to hypoxia. Collectively, we provide evidence for a concerted HIF-1α/MT1-MMP signalling axis that explains the induction of adaptor protein 3BP2 and which may link protein binding partners together and stimulate oncogenic MSC migration. These mechanistic observations support the potential for malignant transformation of MSC within hypoxic tumour stroma and may contribute to evasion of the immune system by a tumour.
format	article
author	Sébastien Proulx-Bonneau Amel Guezguez Borhane Annabi
author_facet	Sébastien Proulx-Bonneau Amel Guezguez Borhane Annabi
author_sort	Sébastien Proulx-Bonneau
title	A concerted HIF-1α/MT1-MMP signalling axis regulates the expression of the 3BP2 adaptor protein in hypoxic mesenchymal stromal cells.
title_short	A concerted HIF-1α/MT1-MMP signalling axis regulates the expression of the 3BP2 adaptor protein in hypoxic mesenchymal stromal cells.
title_full	A concerted HIF-1α/MT1-MMP signalling axis regulates the expression of the 3BP2 adaptor protein in hypoxic mesenchymal stromal cells.
title_fullStr	A concerted HIF-1α/MT1-MMP signalling axis regulates the expression of the 3BP2 adaptor protein in hypoxic mesenchymal stromal cells.
title_full_unstemmed	A concerted HIF-1α/MT1-MMP signalling axis regulates the expression of the 3BP2 adaptor protein in hypoxic mesenchymal stromal cells.
title_sort	concerted hif-1α/mt1-mmp signalling axis regulates the expression of the 3bp2 adaptor protein in hypoxic mesenchymal stromal cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/8bb222aef1044918ad532160a6e6b574
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A concerted HIF-1α/MT1-MMP signalling axis regulates the expression of the 3BP2 adaptor protein in hypoxic mesenchymal stromal cells.

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