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Open AccessReview

Cysteine Cathepsins and Their Extracellular Roles: Shaping the Microenvironment

by 1,2,†, 1,2,†, 1,3,* and 1,4,*
1
Jozef Stefan Institute, Department of Biochemistry and Molecular and Structural Biology, Jamova 39, SI-1000 Ljubljana, Slovenia
2
International Postgraduate School Jozef Stefan, Jamova 39, SI-1000 Ljubljana, Slovenia
3
Department of Biology, Institute of Molecular Systems Biology, ETH Zürich Otto-Stern-Weg 3, 8093 Zürich, Switzerland
4
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Vecna pot 113, SI-1000 Ljubljana, Slovenia
*
Authors to whom correspondence should be addressed.
These authors have contribution equally.
Cells 2019, 8(3), 264; https://doi.org/10.3390/cells8030264
Received: 7 February 2019 / Revised: 12 March 2019 / Accepted: 15 March 2019 / Published: 20 March 2019
(This article belongs to the Special Issue Extracellular Matrix Remodeling)
For a long time, cysteine cathepsins were considered primarily as proteases crucial for nonspecific bulk proteolysis in the endolysosomal system. However, this view has dramatically changed, and cathepsins are now considered key players in many important physiological processes, including in diseases like cancer, rheumatoid arthritis, and various inflammatory diseases. Cathepsins are emerging as important players in the extracellular space, and the paradigm is shifting from the degrading enzymes to the enzymes that can also specifically modify extracellular proteins. In pathological conditions, the activity of cathepsins is often dysregulated, resulting in their overexpression and secretion into the extracellular space. This is typically observed in cancer and inflammation, and cathepsins are therefore considered valuable diagnostic and therapeutic targets. In particular, the investigation of limited proteolysis by cathepsins in the extracellular space is opening numerous possibilities for future break-through discoveries. In this review, we highlight the most important findings that establish cysteine cathepsins as important players in the extracellular space and discuss their roles that reach beyond processing and degradation of extracellular matrix (ECM) components. In addition, we discuss the recent developments in cathepsin research and the new possibilities that are opening in translational medicine. View Full-Text
Keywords: cathepsin; inflammation associated disease; cancer; osteoporosis; extracellular matrix cathepsin; inflammation associated disease; cancer; osteoporosis; extracellular matrix
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MDPI and ACS Style

Vidak, E.; Javoršek, U.; Vizovišek, M.; Turk, B. Cysteine Cathepsins and Their Extracellular Roles: Shaping the Microenvironment. Cells 2019, 8, 264. https://doi.org/10.3390/cells8030264

AMA Style

Vidak E, Javoršek U, Vizovišek M, Turk B. Cysteine Cathepsins and Their Extracellular Roles: Shaping the Microenvironment. Cells. 2019; 8(3):264. https://doi.org/10.3390/cells8030264

Chicago/Turabian Style

Vidak, Eva; Javoršek, Urban; Vizovišek, Matej; Turk, Boris. 2019. "Cysteine Cathepsins and Their Extracellular Roles: Shaping the Microenvironment" Cells 8, no. 3: 264. https://doi.org/10.3390/cells8030264

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