Transmembrane protease serine 4 (TMPRSS4), a type-II transmembrane serine 
protease, is involved in the development and progression of wide range of 
tumors. However, the biological role of TMPRSS4 in prostate cancer remains 
obscure. Here, we investigated the effect of TMPRSS4 on proliferation and 
migration in prostate cancer and potential mechanisms. Our findings demonstrated 
over-expression of TMPRSS4 promoted the PC3 prostate cancer cells migration, 
which could be reversed by TMPRSS4 silencing. TMPRSS4 induced TWIST1 expression 
and followed progression of EMT along with upregulation of N-cadherin and 
downregulation of E-cadherin via STAT3 phosphorylation. Silencing TWIST1 
significantly attenuated TMPRSS4-induced PC3 migration. Moreover, knockdown of 
STAT3 effectively attenuated TMPRSS4-induced TWIST1 expression and TWIST1 
promoter activity. Taken together, we demonstrated a mechanistic cascade of 
TMPRSS4 up-regulating STAT3 activation and subsequent TWIST1 expression, leading 
to prostate cancer migration.