The HGF/SF-induced phosphorylation of paxillin, matrix adhesion, and invasion of prostate cancer cells were suppressed by NK4, an HGF/SF variant.
Hepatocyte growth factor/scatter factor (HGF/SF) plays a crucial role in cancer cell migration, matrix adhesion, invasion, and angiogenesis, via the phosphorylation of the c-met tyrosine kinase. This study examined the ability of NK4, a recently discovered HGF/SF variant, to inhibit the influence of HGF/SF on cell-matrix interaction, paxillin phosphorylation, and invasion of prostate cancer cells. HGF/SF was shown to dramatically enhance tumour cell motility, invasion, cell-matrix adhesion, together with an increase in the degree of paxillin phosphorylation and formation of focal adhesion complexes. However, these HGF/SF-induced effects were suppressed by the presence of NK4. NK4 effectively inhibited the degree of HGF/SF-induced paxillin phosphorylation and matrix adhesion. As a consequence, the matrix invasion of these prostate cancer cells was also suppressed by NK4. In conclusion, this study shows that these HGF/SF-enhanced events, which are critical steps in metastasis, can be inhibited through the addition of NK4, thus warranting further in vivo studies on the implication of NK4 as a potential antimetastasis agent in prostate cancer.
Parr
C
C
Department of Surgery, Department of Oncology, University of Wales College of Medicine, Heath Park, Cardiff, CF14-4XN, United Kingdom. parrc@cardiff.ac.uk
Davies
G
G
Nakamura
T
T
Matsumoto
K
K
Mason
M D
MD
Jiang
W G
WG
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008934:Mitogens; D009361:Neoplasm Invasiveness; D051419:Paxillin; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D000970:Antineoplastic Agents; D003598:Cytoskeletal Proteins; C066855:HGF protein, human; D008934:Mitogens; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D014443:Tyrosine; D017228:Hepatocyte Growth Factor