Cathepsin B and its role(s) in cancer progression.
Experimental and clinical evidence has linked cathepsin B with tumour invasion and metastasis. Cathepsin B expression is increased in many human cancers at the mRNA, protein and activity levels. In addition, cathepsin B is frequently overexpressed in premalignant lesions, an observation that associates this protease with local invasive stages of cancer. Increased expression of cathepsin B in primary cancers, and especially in preneoplastic lesions, suggests that this enzyme might have pro-apoptotic features. Expression of cathepsin B is regulated at many different levels, from gene amplification, use of alternative promoters, increased transcription and alternative splicing, to increased stability and translatability of transcripts. During the transition to malignancy, a change in the localization of cathepsin B occurs, as demonstrated by the presence of cathepsin B-containing vesicles at the cell periphery and at the basal pole of polarized cells. Due to increased expression of cathepsin B and changes in intracellular trafficking, increased secretion of procathepsin B from tumours is observed. Active cathepsin B is also secreted from tumours, a mechanism likely to be facilitated by lysosomal exocytosis or extracellular processing by surface activators. Cathepsin B is localized to caveolae on the tumour surface, where binding to the annexin II heterotetramer occurs. Activation of cathepsin B on the cell surface leads to the regulation of downstream proteolytic cascade(s).
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Izabela
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Podgorski
Bonnie F
BF
Sloane
D017209:Apoptosis / Q000502:physiology; D002401:Cathepsin B / Q000502:physiology*; D018450:Disease Progression; D006801:Humans; D006868:Hydrolysis; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology*; D011230:Precancerous Conditions / Q000201:enzymology / Q000473:pathology
D002401:Cathepsin B