Cathepsin B: Multiple roles in cancer
Top Cited Papers
- 22 February 2014
- journal article
- review article
- Published by Wiley in Proteomics – Clinical Applications
- Vol. 8 (5-6), 427-437
- https://doi.org/10.1002/prca.201300105
Abstract
Proteases, including intracellular proteases, play roles at many different stages of malignant progression. Our focus here is cathepsin B, a lysosomal cysteine cathepsin. High levels of cathepsin B are found in a wide variety of human cancers, levels that often induce secretion and association of cathepsin B with the tumor cell membrane. In experimental models, such as transgenic models of murine pancreatic and mammary carcinomas, causal roles for cathepsin B have been demonstrated in initiation, growth/tumor cell proliferation, angiogenesis, invasion, and metastasis. Tumor growth in transgenic models is promoted by cathepsin B in tumor‐associated cells, for example, tumor‐associated macrophages, as well as in tumor cells. In transgenic models, the absence of cathepsin B has been associated with enhanced apoptosis, yet cathepsin B also has been shown to contribute to apoptosis. Cathepsin B is part of a proteolytic pathway identified in xenograft models of human glioma; targeting only cathepsin B in these tumors is less effective than targeting cathepsin B in combination with other proteases or protease receptors. Understanding the mechanisms responsible for increased expression of cathepsin B in tumors and association of cathepsin B with tumor cell membranes is needed to determine whether targeting cathepsin B could be of therapeutic benefit.Keywords
Funding Information
- National Institutes of Health (R01 CA131990)
This publication has 157 references indexed in Scilit:
- The metalloproteases meprin α and meprin β: unique enzymes in inflammation, neurodegeneration, cancer and fibrosisBiochemical Journal, 2013
- uPAR and cathepsin B shRNA impedes TGF-β1-driven proliferation and invasion of meningioma cells in a XIAP-dependent pathwayCell Death & Disease, 2012
- Live-cell imaging of tumor proteolysis: Impact of cellular and non-cellular microenvironmentBiochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2012
- Proteases involved in cartilage matrix degradation in osteoarthritisBiochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2012
- RETRACTED ARTICLE: uPAR and cathepsin B downregulation induces apoptosis by targeting calcineurin A to BAD via Bcl-2 in gliomaJournal of Neuro-Oncology, 2011
- Balancing act: deubiquitinating enzymes in the nervous systemTrends in Neurosciences, 2011
- Protective role of cathepsin L in mouse skin carcinogenesisMolecular Carcinogenesis, 2011
- Pleiotropic roles of matrix metalloproteinases in tumor angiogenesis: Contrasting, overlapping and compensatory functionsBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2010
- Deficiency for the cysteine protease cathepsin L promotes tumor progression in mouse epidermisOncogene, 2009
- Membrane type 1-matrix metalloproteinase: Substrate diversity in pericellular proteolysisSeminars in Cell & Developmental Biology, 2008