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2015 ; 112
(1
): 4-8
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TMPRSS4: an emerging potential therapeutic target in cancer
#MMPMID25203520
de Aberasturi AL
; Calvo A
Br J Cancer
2015[Jan]; 112
(1
): 4-8
PMID25203520
show ga
Altered expression and activity of proteases is a key event in cancer,
particularly in relation to invasion, modification of the extracellular matrix
and metastasis. The transmembrane protease, serine 4 (TMPRSS4) is closely related
to other cancer-associated proteases, such as hepsin, TMPRSS2 and matriptase. We
review in this study up-to-date information about expression, role, regulation
and clinical relevance of TMPRSS4 in cancer. Increased expression of this
protease is associated with acquisition of epithelial to mesenchymal transition,
invasion and metastasis in vivo. Signalling in cancer cells involves upregulation
of integrin-?5 (ITG-?5) and urokinase-type plasminogen activator (uPA),
downregulation of E-cadherin and activation of uPA enzymatic activity at the
plasma membrane, as well as phosphorylation of FAK, Src, Akt and ERK1/2
intracellularly. Upregulation of miR-205 hinders the protumorigenic effects
elicited by TMPRSS4 through restoration of E-cadherin levels and direct targeting
of ITG-?5. High levels of TMPRSS4 have been found in several types of solid
tumours in patients, and association with poor prognosis has been consistently
described. On the basis of this information and the structural characteristics of
this druggable protease, we suggest that TMPRSS4 could be a novel potential
therapeutic target in solid tumours.