title: Dual roles of protein tyrosine phosphatase kappa in coordinating angiogenesis induced by pro-angiogenic factors.
abstract: A potential role may be played by receptor-type protein tyrosine phosphatase kappa (PTPRK) in angiogenesis due to its critical function in coordinating intracellular signal transduction from various receptors reliant on tyrosine phosphorylation. In the present study, we investigated the involvement of PTPRK in the cellular functions of vascular endothelial cells (HECV) and its role in angiogenesis using in vitro assays and a PTPRK knockdown vascular endothelial cell model. PTPRK knockdown in HECV cells (HECVPTPRKkd) resulted in a decrease of cell proliferation and cell-matrix adhesion; however, increased cell spreading and motility were seen. Reduced focal adhesion kinase (FAK) and paxillin protein levels were seen in the PTPRK knockdown cells which may contribute to the inhibitory effect on adhesion. HECVPTPRKkd cells were more responsive to the treatment of fibroblast growth factor (FGF) in their migration compared with the untreated control and cells treated with VEGF. Moreover, elevated c-Src and Akt1 were seen in the PTPRK knockdown cells. The FGF-promoted cell migration was remarkably suppressed by an addition of PLCγ inhibitor compared with other small inhibitors. Knockdown of PTPRK suppressed the ability of HECV cells to form tubules and also impaired the tubule formation that was induced by FGF and conditioned medium of cancer cells. Taken together, it suggests that PTPRK plays dual roles in coordinating angiogenesis. It plays a positive role in cell proliferation, adhesion and tubule formation, but suppresses cell migration, in particular, the FGF-promoted migration. PTPRK bears potential to be targeted for the prevention of tumour associated angiogenesis.
authors.affiliation: Cardiff China Medical Research Collaborative Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Ping-Hui
authors.initials: PH
authors.lastname: Sun
authors.affiliation: Cardiff China Medical Research Collaborative Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Cardiff China Medical Research Collaborative Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Mason
authors.affiliation: Cardiff China Medical Research Collaborative Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: Cardiff China Medical Research Collaborative Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C496061:PXN protein, human; D051419:Paxillin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D000081247:CSK Tyrosine-Protein Kinase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; C000631346:CSK protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; C489852:PTPRK protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2