The cathepsin family and their role in colorectal cancer.
Cathepsins are a class of globular proteases, initially described as intracellular peptide hydrolases, although several cathepsins also have extracellular functions. Cathepsins B, C, F, H, L, K, O, S, V, W, and X are cysteine proteases of the papain family, and represent the largest and best-known class of the cathepsins. Cathepsin G is a serine carboxypeptidases, and cathepsins D and E are aspartic proteases. Cathepsins are synthesized as inactive proenzymes and processed to become mature and active enzymes. Endogenous protein inhibitors, such as cystatins and some serpins, inhibit active enzymes. As primarily lysosomal proteases, cathepsins play important roles in proteolysis during physiological processes, as well as in several diseases. On the basis of their ability to degrade extracellular matrix proteins, cathepsins have been implicated to play a role in invasion and metastasis of colorectal cancer. In the present review, the role of cathepsins in the disease process of colorectal cancers and the correlation of cathepsin expression and activity with clinicopathological features is discussed. Furthermore, we give an overview of the recent developments of cathepsins in animal models and in in vitro experiments of colorectal disease, and provide information on inhibitors of cathepsins as possible therapeutics.
Kuester
Doerthe
D
Department of Pathology, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany.
Lippert
Hans
H
Roessner
Albert
A
Krueger
Sabine
S
D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000502:physiology*; D002478:Cells, Cultured; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D009362:Neoplasm Metastasis; D011379:Prognosis
D004791:Enzyme Inhibitors; D002403:Cathepsins