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).
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Jeremy Saklatvala; Hideaki Nagase; Guy Salvesen
Conference Article| September 01 2003
Cathepsin B and its role(s) in cancer progression
Izabela Podgorski ;
Biochem Soc Symp (2003) 70: 263–276.
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Jeremy Saklatvala, Hideaki Nagase, Guy Salvesen, Izabela Podgorski, Bonnie F. Sloane; Cathepsin B and its role(s) in cancer progression. Biochem Soc Symp 1 September 2003; 70 263–276. doi: https://doi.org/10.1042/bss0700263
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