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

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Cysteine cathepsins (Cts) are lysosomal proteases involved in intracellular protein degradation.
• They are synthesized as zymogens and activated autocatalytically, with activity regulated by inhibitors.
• Cts can be secreted, playing a role in extracellular matrix (ECM) remodeling and tumor progression.

Purpose of the Study:

• To investigate the multifaceted roles of cysteine cathepsins in cancer development.
• To elucidate the mechanisms by which Cts contribute to neoplastic transformation, invasion, and metastasis.
• To understand the regulatory and destructive functions of Cts in both intracellular and extracellular environments.

Main Methods:

• Review of existing literature on cysteine cathepsin function in cellular processes and cancer.
• Analysis of studies detailing Cts expression, activity, and regulation in various cancer types.
• Examination of research on Cts involvement in signaling pathways like RTK/MAPK, Wnt, Notch, and TGF-β.

Main Results:

• Cts expression and activity significantly increase in cancer cells and the extracellular space, correlating with tumor progression.
• Extracellular Cts hydrolyze ECM proteins, remodel the ECM, and process signaling molecules.
• Cts influence cancer development by modulating growth factor signaling pathways and promoting epithelial-mesenchymal transition (EMT).

Conclusions:

• Cysteine cathepsins exhibit both destructive proteolytic and regulatory functions in cancer.
• Their altered expression and activity are critical drivers of neoplastic transformation, invasion, and metastasis.
• Cts impact cancer progression through direct ECM degradation and indirect modulation of key signaling pathways.