Proteases and cancer development

Dysfunction of proteases is observed in many cancers. Signaling and functional roles of both intracellular proteases and extracellular proteases in the development of cancer are discussed in this chapter. As mitochondrial proteases, HtrA2/Omi regulates inhibitors of apoptosis proteins, while Lon protease degrades misfolded proteins and maintains the stability of the mitochondrial genome. Caspases are closely interconnected with mitochondria in apoptosis and serve as the major executors of the apoptosis machinery. Cathepsin proteases have multiple substrates including growth factors and extracellular matrix proteins. Matrix metalloproteinases trigger the release of growth and angiogenic factors and modulate extracellular matrix molecules. Changes of these proteases affect various aspects of cancer development, including transformation, apoptosis, invasion, and metastasis of cancer cells. Targeting these proteases is becoming an important approach to cancer treatment.