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.