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 in
- PDF / 356,134 Bytes
- 17 Pages / 439.37 x 666.14 pts Page_size
- 25 Downloads / 222 Views
Proteases and Cancer Development Shudong Zhu and Zhoufang Li
Abstract 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. Keywords Protease • Cancer • Mitochondria • Caspase • Cathepsin • Matrix metalloproteinase • Apoptosis • Invasion • Metastasis
1
Introduction
Proteases are responsible for proteolysis, one of the most fundamental posttranslational regulatory systems. They are involved in various physiological processes. Dysfunction of proteases is observed in many cancers. Here we will discuss both These authors contributed equally to this work. S. Zhu (*) Department of Biochemistry, School of Life Sciences, XiangYa School of Medicine, Central South University, Chang Sha, Hu Nan, China e-mail: [email protected] Z. Li Department of Biology, South University of Science and Technology of China, Shenzhen, China N.S. Dhalla and S. Chakraborti (eds.), Role of Proteases in Cellular Dysfunction, Advances in Biochemistry in Health and Disease 8, DOI 10.1007/978-1-4614-9099-9_7, © Springer Science+Business Media New York 2014
129
130
S. Zhu and Z. Li
Fig. 7.1 Network of intracellular and extracellular proteases in cancer development. MMP matrix metalloproteinases, HtrA2/Omi high temperature requirement protein A2, HIF hypoxia-inducible factor, COX cytochrome C oxidase, MOMP major outer membrane protein, IAP inhibitors of apoptosis proteins, WT1 Wilms’ tumor suppressor protein
intracellular proteases and extracellular proteases in cancer development, including mitochondrial proteases, lysosome proteases, cytosolic proteases, and matrix metalloproteinases (MMPs). Figure 7.1 shows the network of the proteases in cancer development (Fig. 7.1).
2
Mitochondrial Proteases in Cancers
Mitochondria are essential for the survival and proliferation of normal and cancer cells. Besides their role as an energy factory for maintaining metabolism and proliferation of cells, they are also part of the apoptosis machinery. Dysfunction of mitochondria may lead to the development of various cancers. Mitochondrial proteases play crucial roles in cancer development directly or indirectly. Some of them strictly control
Data Loading...
