Human DESC1 serine protease confers tumorigenic properties to MDCK cells and it is upregulated in tumours of different origin.
Proteolysis of the extracellular matrix components plays a crucial role in the regulation of the cellular and physiological processes, and different pathologies have been associated with the loss or gain of function of proteolytic enzymes. DESC1 (differentially expressed in squamous cell carcinoma gene 1), a member of the TTSP (type II transmembrane serine protease) family of serine proteases, is an epithelial-specific enzyme that has been found downregulated in squamous cell carcinoma of the head and neck region. We describe new properties of DESC1 suggesting that this protease may be involved in the progression of some type of tumours. Thus, this enzyme hydrolyses some extracellular matrix components, such as fibronectin, gelatin or fibrinogen. Moreover, Madin-Darby canine kidney (MDCK) cells expressing exogenous human DESC1 acquire properties associated with tumour growth such as enhanced motility and an increase of tubular forms in a 3D collagen lattice following HGF treatment. Finally, we generated polyclonal anti-DESC1 antibodies and immunohistochemical analysis in tissues different from head and neck region indicated that this protease was overexpressed in tumours of diverse origins. Taken together, our results suggest that DESC1 could be considered as a potential therapeutic target in some type of tumours.
Viloria
C G
CG
Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, 33006, Asturias, Spain.
Peinado
J R
JR
Astudillo
A
A
García-Suárez
O
O
González
M V
MV
Suárez
C
C
Cal
S
S
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002384:Catalysis; D002462:Cell Membrane / Q000201:enzymology; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D015854:Up-Regulation
D000906:Antibodies; D008565:Membrane Proteins; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; C524420:TMPRSS11E protein, human