The Role of Peptidases in Cancer

Dear Colleagues,

Proteases catalyze the hydrolysis of peptide bonds and are classified into seven major types based on their catalytic mechanisms and specific residues involved in their catalytic domains, such as aspartic acid (aspartic proteases), cysteine (cysteine proteases), metal ion (metalloproteinases), serine (serine proteases), threonine (threonine proteases), glutamate (glutamic proteases), and hybrid or unknown residues (other proteases). 

Proteases play critical and diverse roles in normal physiology due to their proteolytic function of degrading, inactivating, or activating proteins within multiple biological processes. Proteases can also serve as signaling molecules by catalyzing specific peptide bonds that trigger varied cellular responses, such as DNA replication, cell cycle progression, cell proliferation, differentiation, cell motility, and cell death, across all cell types and diseases, including cancer. 

The dysregulated expression and activity of proteases from the different protease families are involved in the development and progression of cancer. Proteases increase the invasive phenotype of cancer cells by degrading extracellular matrix proteins, facilitating the epithelial–mesenchymal transition, resisting apoptosis, and promoting immune suppression and metastasis development. Proteases also contribute to cancer-driving signaling pathways, such as mitogen-activated protein kinase (MAPK), protein kinase B (Akt), tumor necrosis factor b (TNF-β), etc. As knowledge of cancer-associated proteases and their regulation and functions expands, they become attractive targets for the development of diagnostic and therapeutic technologies aimed at cancer detection and the suppression of neoplastic transformation. Because the proteolytic landscape of cancer is complex and involves converging substrates, this presents a challenge for developing clinically relevant therapeutic strategies targeting these proteases, but it also offers opportunities for finding new approaches for precision medicine.

This Special issue invites original research articles and comprehensive reviews focused on the newest findings on and advances in our understanding of protease-mediated molecular pathways in cancer and their clinical implications.

Dr. Natalia A. Ignatenko
Guest Editor

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