Human DESC1 serine protease confers tumorigenic properties to MDCK cells and it is upregulated in tumours of different origin

Abstract

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.

Membrane-Anchored Serine Proteases in Health and Disease

“…240 Madin-Darby canine kidney (MDCK) cells expressing exogenous human DESC1 display enhanced motility and an increase of tubular forms in a three-dimensional collagen lattice following HGF treatment. 241 Kinetic studies using internally quenched peptides 227,242 and structural analyses of the DESC1 catalytic domain 23 reveal DESC1 substrate preference for large hydrophobic residues in P 4 /P 3 , for small residues in P 2 , Arg or Lys in P 1 , and hydrophobic residues in P 1 0 and P 3 0 . Mouse DESC1 forms stable inhibitory complexes with PAI-1 and PCI, suggesting that these serpins might be regulators of DESC1 proteolytic activities in DESC1 expressing tissues.…”

Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis

“…41 Interestingly, overexpression of DESC1 has been documented in tumors derived from kidney, brain and breast tissues, suggesting a pro-tumorigenic function depending on the tissue of origin. 47 The second largest of the sub-families, hepsin/ TMPRSS/enteropeptidase contains TMPRSS 2-5, [48][49][50] MSPL, 51 hepsin and enteropeptidase. The most comprehensively described member of this sub-family, enteropeptidase, functions near the apex of a proteolytic cascade of digestive enzymes through its conversion of trypsinogen to trypsin.…”

Frequent decreased expression of candidate tumor suppressor gene, DEC1, and its anchorage‐independent growth properties and impact on global gene expression in esophageal carcinoma

“…30 An oncogenic role of DESC1 was suggested by high DESC1 expression in kidney, brain and breast cancers and the observation of tumorigenic properties in MadinDarby canine kidney cells after its overexpression. 31 Significant correlation of KLK11 expression and poor patient survival in epithelial ovarian cancer suggests that KLK11 may participate in cancer development. 32 Taken together, global expression alterations associated with DEC1 expression identified several interesting possible candidate TSGs and oncogenes that may play a role in the development of this cancer.…”