‘Patchiness’ and basic cancer research: unravelling the proteases

Abstract

The recent developments in Cathepsin protease research have unveiled a number of key observations which are fundamental to further our understanding of normal cellular homeostasis and disease. By far, the most interesting and promising area of Cathepsin biology stems from how these proteins are linked to the fate of living cells through the phenomenon of Lysosomal Leakage and Lysosomal Membrane Permeabilisation. While extracellular Cathepsins are generally believed to be of central importance in tumour progression, through their ability to modulate the architecture of the Extracellular Matrix, intracellular Cathepsins have been established as being of extreme significance in mediating cell death through Apoptosis. With these two juxtaposed key research areas in mind, the focus of this review highlights recent advancements in how this fastpaced area of Cathepsin research has recently evolved in the context of their mechanistic regulation in cancer research.

The Potential Role of Cathepsin K in Non-Small Cell Lung Cancer

“…In contrast, the migration and invasion ability of CTSK -KD was significantly reduced. This is consistent with the conclusion that Cathepsin K is highly expressed during tumor invasion and metastasis [ 39 ] and has a stimulating effect on the aggressive phenotype of various types of cancer. Soond et al [ 40 ] reported that the findings of use of utilizes combined chemotherapeutic treatment such as with Tocilizumab or Rituximab inhibited signaling transduction pathways which up-regulate the intracellular Cathepsins look very encouraging for targeting cancer.…”

Current Status and Perspectives of Protease Inhibitors and Their Combination with Nanosized Drug Delivery Systems for Targeted Cancer Therapy

“…Thus, they can act as the base for membrane and matrix degradation, inactivation of natural protease inhibitors and chemotherapeutics, cell viability regulation, immune response modulation and inflammatory cell recruitment. [15][16][17][18] Moreover, proteases localized within the intracellular compartments, including in the cytosol, nucleus, membrane and mitochondria are associated with many signaling pathways through which they can promote: adhesion, proliferation, migration, de-differentiation and epithelial to mesenchymal transition of cancer cells. [18][19][20] The release of proteases into various cellular compartments and their altered expression can result from different factors, including the activation of membrane receptors (such as the tumor necrosis factor receptor 21 ) or the generation of reactive oxygen species.…”

Is There a Trojan Horse to Aggressive Pancreatic Cancer Biology? A Review of the Trypsin-PAR2 Axis to Proliferation, Early Invasion, and Metastasis

“…The premature activation or, even intracellular activation, of other types of proteases has been demonstrated to be important mechanism to disease states through mechanisms hitherto poorly understood or scarcely investigated. 9 Premature release and activation in the cell or leaks of trypsin into the stroma may facilitate activation of enzyme cascades, leading to cellular proliferation, migration, invasion, angiogenesis, and metastasis ( Fig. 1).…”