J. Cancer Mol. 2: 183-190, 2006

[Review Article]

Matrix-Degrading Type II Transmembrane Serine Protease Matriptase: Its Role in Cancer Development and Malignancy

Ming-Shyue Lee

Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, and Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA

 Abstract: 

Proteolysis on the cell surface has well-known roles in the tissue homeostasis and in the pathogenesis such as cancers.  A newly described, epithelia-derived type II transmembrane serine protease, matriptase, has been shown with important roles in the epithelial homeostasis, i.e., terminal keratinocyte differentiation, as well as its deregulation in the cancer development and progression.  In epithelia, matriptase has a cognate inhibitor HAI-1 (hepatocyte growth factor activator inhibitor-1) for the regulation of this protease expression, trafficking, and activity.  In animal model, matriptase is essential for postnatal survival, epidermal barrier function, stratum corneum, and hair follicle development, as well as thymocyte survival.  Deregulated matriptase induces carcinogenesis and malignant transformation.  In human cancers, both matriptase and HAI-1 expression are recurrently lost of their balance, resulting in activation of the protease, which is correlated with clinical stages.  Thus, malfunction of matriptase potently raises cancer development and metastatic cancer lesions. 

Received 9/28/06; Revised 10/14/06; Accepted 10/16/06.

¹Correspondence: Dr. Ming-Shyue Lee, Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road Section 1, Taipei 100, Taiwan. Phone: 886-2-2395 7966. Fax: 886-2-2391 5295. Email: mslee@ha.mc.ntu.edu.tw 

²Abbreviations: ECM, extracellular matrix; MMP, matrix metalloprotease; uPA, urokinase-type plasminogen activator; TTSP, type II transmembrane serine protease; HAI-1, hepatocyte growth factor activator inhibitor-1; SEA, Sperm protein-Enterokinase-Agrin; CUB, C1r/s-Uegf-Bone morphogenic protein-1; LDL, low-density lipoprotein; KD, Kunitz domain; MoAb, monoclonal antibody; S1P, sphingosine 1-phosphate; PAR-2, protease-activated receptor-2.