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NDRG1 and CRK-I/II are regulators of endothelial cell migration under intermittent hypoxia

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Abstract

Intermittent Hypoxia (IH) that develops in neovascularized solid tumours has been described to positively influence the tumour growth by modulating the behaviour of cancer cells as well as of endothelial cells. However, the molecular mechanisms regulated by IH still remain poorly understood. In this work, the effects of IH were investigated on endothelial cells by a proteomic approach. Protein abundance variations were studied using fluorescent 2D-Differential in Gel Electrophoresis (2D-DIGE). Amongst the proteins of which the abundance varied under IH, NDRG1 and CRK-I/II were identified by mass spectrometry. These proteins have already been described to influence cancer cell migration as well as the angiogenic processes in solid tumours. Since an increase in endothelial cell migration under IH was evidenced in our previous work, the involvement of NDRG1 and CRK-I/II proteins in endothelial cell migration under IH was determined by silencing the expression of both proteins using siRNA. The results revealed that NDRG1 and CRK-I/II are indeed regulators of endothelial cell migration under intermittent hypoxia: silencing of CRK-I/II resulted in an increase in endothelial cell migration, whereas the invalidation of NDRG1 decreased it. These results give news insight regarding the effects of IH on endothelial cell migration and hence on neoangiogenesis.

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Acknowledgments

Sébastien Toffoli is recipient of a FNRS-Télévie grant. Carine Michiels is research director of FNRS and Olivier Feron is senior research associate of FNRS (Fonds National de la Recherche Scientifique, Belgium). This article presents results of the Belgian Program on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister’s Office, Science Policy Programming. The responsibility is assumed by its authors.

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Authors and Affiliations

  1. Laboratory of Biochemistry and Cellular Biology, FUNDP-University of Namur, 61 rue de Bruxelles, 5000, Namur, Belgium

    Sébastien Toffoli, Edouard Delaive, Marc Dieu, Martine Raes & Carine Michiels

  2. University of Louvain Medical School, Unit of Pharmacology and Therapeutics, UCL-FATH 5349, 53 Avenue E. Mounier, 1200, Brussels, Belgium

    Olivier Feron

Authors
  1. Sébastien Toffoli
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  2. Edouard Delaive
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  3. Marc Dieu
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  4. Olivier Feron
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  5. Martine Raes
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  6. Carine Michiels
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Correspondence to Carine Michiels.

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Toffoli, S., Delaive, E., Dieu, M. et al. NDRG1 and CRK-I/II are regulators of endothelial cell migration under intermittent hypoxia. Angiogenesis 12, 339–354 (2009). https://doi.org/10.1007/s10456-009-9156-2

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  • DOI: https://doi.org/10.1007/s10456-009-9156-2

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