PMID- 11478803 OWN - NLM STAT- MEDLINE DCOM- 20010913 LR - 20240514 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 285 IP - 5 DP - 2001 Aug 3 TI - The HGF/SF-induced phosphorylation of paxillin, matrix adhesion, and invasion of prostate cancer cells were suppressed by NK4, an HGF/SF variant. PG - 1330-7 AB - 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. CI - Copyright 2001 Academic Press. FAU - Parr, C AU - Parr C AD - Department of Surgery, Department of Oncology, University of Wales College of Medicine, Heath Park, Cardiff, CF14-4XN, United Kingdom. parrc@cardiff.ac.uk FAU - Davies, G AU - Davies G FAU - Nakamura, T AU - Nakamura T FAU - Matsumoto, K AU - Matsumoto K FAU - Mason, M D AU - Mason MD FAU - Jiang, W G AU - Jiang WG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Antineoplastic Agents) RN - 0 (Cytoskeletal Proteins) RN - 0 (HGF protein, human) RN - 0 (Mitogens) RN - 0 (PXN protein, human) RN - 0 (Paxillin) RN - 0 (Phosphoproteins) RN - 42HK56048U (Tyrosine) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Antineoplastic Agents/pharmacology MH - Blotting, Western MH - Cell Adhesion/drug effects MH - Cell Division/drug effects MH - Cell Movement/*drug effects MH - Cytoskeletal Proteins/analysis/*metabolism MH - Extracellular Matrix/*metabolism MH - Fluorescent Antibody Technique MH - Hepatocyte Growth Factor/antagonists & inhibitors/*pharmacology MH - Humans MH - Male MH - *Mitogens MH - Neoplasm Invasiveness MH - Paxillin MH - Phosphoproteins/analysis/*metabolism MH - Phosphorylation/drug effects MH - Prostatic Neoplasms/*drug therapy/*metabolism/pathology MH - Tumor Cells, Cultured MH - Tyrosine/metabolism EDAT- 2001/08/02 10:00 MHDA- 2001/09/14 10:01 CRDT- 2001/08/02 10:00 PHST- 2001/08/02 10:00 [pubmed] PHST- 2001/09/14 10:01 [medline] PHST- 2001/08/02 10:00 [entrez] AID - S0006-291X(01)95307-0 [pii] AID - 10.1006/bbrc.2001.5307 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2001 Aug 3;285(5):1330-7. doi: 10.1006/bbrc.2001.5307.