title: NDRG1 and CRK-I/II are regulators of endothelial cell migration under Intermittent Hypoxia.
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.
authors.affiliation: Laboratory of Biochemistry and Cellular Biology, FUNDP-University of Namur, Namur, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Toffoli
authors.forename: Edouard
authors.initials: E
authors.lastname: Delaive
authors.forename: Marc
authors.initials: M
authors.lastname: Dieu
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.forename: Martine
authors.initials: M
authors.lastname: Raes
authors.forename: Carine
authors.initials: C
authors.lastname: Michiels
mesh_terms: D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D002461:Cell Line, Transformed / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement; D004334:Drug Administration Schedule; D015180:Electrophoresis, Gel, Two-Dimensional; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D013058:Mass Spectrometry; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D040901:Proteomics; D050737:Proto-Oncogene Proteins c-crk / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010100:Oxygen; D050737:Proto-Oncogene Proteins c-crk; D034741:RNA, Small Interfering; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C485285:CRK protein, human