J. Cancer Mol.
3: 5-14, 2007
[Review
Article]
Lysosomal Cysteine Proteinase Cathepsin S as a Potential Target for
Anti-Cancer Therapy
Wun-Shaing W. Chang1, Hsin-Ru Wu, Chi-Tai Yeh, Cheng-Wen
Wu, and Jang-Yang Chang
National Institute of Cancer Research, National Health Research
Institutes, Zhunan, Taiwan
Abstract:
In mammalian cells, cysteine proteinases are localized mainly in the
cytoplasm and lysosomal compartments. For lysosomal cysteine
proteinases, they are synthesized as inactive zymogens and converted
to active forms occurred in the acidic and reducing conditions of late
endosomes or lysosomes. Here we review the roles of active lysosomal
cysteine proteinases in particular cathepsin S and its importance to
many physiological or pathological processes including tumor growth,
angiogenesis, and metastasis. Biochemical and clinical studies have
shown significant changes in the levels of mRNA expression and enzyme
activity of cathepsin S in various cancer tissues and cell lines.
Immunologic, molecular and pharmaceutical approaches to alter the
expression and proteolytic activity of cathepsin S all provided strong
evidence for a causal role of this proteolytic enzyme in tumor
progression and invasion. Determination of the X-ray structures of
either cathepsin S alone or complexed with inhibitors further offered
insights of the active site pocket of cathepsin S, thereby making the
rational design of low-molecular weight synthetic inhibitors feasible
for anti-cancer drug development and treatment.
(Keywords: migration;
invasion; metastasis; cysteine proteinase; cathepsin S)
___________________________________________________________________________________
Received 1/24/07; Revised 2/13/07; Accepted 2/13/07.
1Correspondence:
Dr. Wun-Shaing Wayne Chang, National
Institute of Cancer Research,
National Health Research Institutes, No. 35, Keyan Road, Zhunan Town,
Miaoli County 350, Taiwan.
Phone: 886-37-246 166 ext 31702. Fax: 886-37-586 463. E-mail:
wayne@nhri.org.tw
2Abbreviations:
ECM, extracellular matrix;
MHCII, major
histocompatibility complex
class II; CLIP, class II invariant chain peptide; HLA-DM, human
leukocyte antigen DM.
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