title: The influence of matriptase-2 on prostate cancer in vitro: a possible role for β-catenin.
abstract: The type II transmembrane serine proteases (TTSPs) are a family of cell             surface proteolytic enzymes contributing to a number of processes, such as tumour             invasion and metastasis. Within the TTSPs, matriptase-2 is a relatively newly             identified member and this protease has been shown to play a key role in cancer             progression. β-catenin has long been regarded as an oncogene. The deregulation             of the β-catenin signalling pathway plays a significant role in the progression             and possibly the development of cancer. However, little is known about the role             of matriptase-2 in prostate cancer. This study aimed to examine the correlation             between matriptase-2 and β-catenin. Matriptase-2 was knocked down in the normal             prostate cells, PZHPV7 and PNT2C2, using a ribozyme transgene targeting matriptase-2.             The altered cells were used in a number of in vitro experiments designed to investigate             the involvement of matriptase-2 with β-catenin and to further characterise its             function. The knockdown of matriptase-2 had no effect on cell growth or adhesion             but significantly reduced cell motility (PZHPV7 cells, p<0.001; PNT2C2 cells,             p=0.001 vs. respective control cells) and invasive capability (PZHPV7 cells, p=0.001;             PNT2C2 cells, p=0.007). The knockdown also caused a large increase in β-catenin             protein expression at the cell membrane in PZHPV7 and PNT2C2 cells and a decrease             in PC3 cells overexpressing matriptase-2, but did not affect the mRNA levels.             Matriptase-2 may have an important impact on prostate cancer progression. The             data gained from this study suggest that matriptase-2 protects against the development             and progression of prostate cancer by regulating the motility and invasive capabilities             of prostate cancer cells. Matriptase-2 also reduces the levels of β-catenin at             the cell membrane. As β-catenin is highly involved in the regulation of cellular             processes, including motility and invasion, the reduction of β-catenin expression             by matriptase-2 may be a possible mechanism by which matriptase-2 functions.
authors.affiliation: Metastasis and Angiogenesis Research Group, Institute of Cancer                     and Genetics, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Siobhan L
authors.initials: SL
authors.lastname: Webb
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sanders
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D001483:Base Sequence; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D051176:beta Catenin; D012697:Serine Endopeptidases; C467801:matriptase 2