title: Matrix metalloproteinases in stem cell regulation and cancer.
abstract: Since Gross and Lapiere firstly discovered matrix metalloproteinases (MMPs) as important collagenolytic enzymes during amphibian tadpole morphogenesis in 1962, this intriguing family of extracellular proteinases has been implicated in various processes of developmental biology. However, the pathogenic roles of MMPs in human diseases such as cancer have also garnered widespread attention. The most straightforward explanation for their role in cancer is that MMPs, through extracellular matrix degradation, pave the way for tumor cell invasion and metastasis. While this notion may be true for many circumstances, we now know that, depending on the context, MMPs may employ additional modes of functionality. Here, we will give an update on the function of MMPs in development and cancer, which may directly regulate signaling pathways that control tissue homeostasis and may even work in a non-proteolytic manner. These novel findings about the functionality of MMPs have important implications for MMP inhibitor design and may allow us to revisit MMPs as drug targets in the context of cancer and other diseases.
authors: Department of Anatomy and Biomedical Sciences Program, University of California, San Francisco, CA 94143-0452, United States.
authors: Kai
authors: K
authors: Kessenbrock
authors: Department of Anatomy and Biomedical Sciences Program, University of California, San Francisco, CA 94143-0452, United States; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Chih-Yang
authors: CY
authors: Wang
authors: Department of Anatomy and Biomedical Sciences Program, University of California, San Francisco, CA 94143-0452, United States. Electronic address: zena.werb@ucsf.edu.
authors: Zena
authors: Z
authors: Werb
mesh_terms: D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D055153:Stem Cell Niche; D013234:Stem Cells / Q000201:enzymology / Q000502:physiology*
chemical_list: D020782:Matrix Metalloproteinases
keywords: Cancer; Cell differentiation; Hemopexin domain; Invasion; Stem cell niche