Cysteine cathepsins: structure, physiological functions and their role in carcinogenesis

Gureeva T.A.1, Timoshenko O.S.1, Kugaevskaya E.V.1, Solovyova N.I.1

1. Institute of Biomedical Chemistry, Moscow, Russia
Section: Review
DOI: 10.18097/PBMC20216706453      PubMed Id: 34964439
Year: 2021  Volume: 67  Issue: 6  Pages: 453-464
Cysteine cathepsins (Cts) also known as thiol proteinases belong to the superfamily of cysteine proteinases (EC 3.4.22). Cts are known as lysosomal proteases responsible for the intracellular proteins degradation. All Cts are synthesized as zymogens, activation of which occurs autocatalytically. Their activity is regulated by endogenous inhibitors. Cts can be secreted into the extracellular environment, which is of particular importance in tumor progression. Extracellular Cts not only hydrolyze extracellular matrix (ECM) proteins, but also contribute to ECM remodeling, processing and/or release of cell adhesion molecules, growth factors, cytokines and chemokines. In cancer, the expression and activity of Cts sharply increase both in cell lysosomes and in the intercellular space, which correlates with neoplastic transformation, invasion, metastasis and leads to further tumor progression. It has been shown that Cts expression depends on the cells type, therefore, their role in the tumor development differs depending on their cellular origin. The mechanism of Cts action in cancer is not limited only by their proteolytic action. The Cts influence on signal transduction pathways associated with cancer development, including the pathway involving growth factors, which is mediated through receptors tyrosine kinases (RTK) and various signaling mitogen-activated protein kinases (MAPK), has been proven. In addition, Cts are able to promote the epithelial-mesenchymal transition (EMT) by activating signal transduction pathways such as Wnt, Notch, and the pathway involving TGF-β. So, Ctc perform specific both destructive and regulatory functions, carrying out proteolysis, both inside and outside the cell.
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Keywords: cysteine cathepsins, lysosomal proteinases, carcinogenesis

Gureeva, T. A., Timoshenko, O. S., Kugaevskaya, E. V., Solovyova, N. I. (2021). Cysteine cathepsins: structure, physiological functions and their role in carcinogenesis. Biomeditsinskaya Khimiya, 67(6), 453-464.
This paper is also available as the English translation: 10.1134/S1990750822020056
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