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Published on: August 21, 2019
Matrix metalloproteinases in stem cell regulation and cancer
Kai Kessenbrock1, Chih-Yang Wang2, Zena Werb1
1Department of Anatomy and Biomedical Sciences Program, University of California, San Francisco, CA 94143-0452, United States.
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.
Insights
Matrix metalloproteinases (MMPs) are crucial in development and cancer. Beyond matrix degradation, MMPs regulate signaling pathways and function non-proteolytically, offering new therapeutic targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Developmental Biology
Background:
- Matrix metalloproteinases (MMPs), discovered in 1962, are extracellular proteinases involved in development.
- MMPs are increasingly recognized for their roles in human diseases, particularly cancer.
Purpose of the Study:
- To provide an updated overview of MMP functions in development and cancer.
- To highlight novel non-proteolytic and signaling pathway regulatory roles of MMPs.
Main Methods:
- Literature review and synthesis of existing research on MMPs.
- Analysis of studies investigating MMPs in developmental processes and tumorigenesis.
Main Results:
- MMPs contribute to tissue homeostasis through both proteolytic and non-proteolytic mechanisms.
- MMPs can directly regulate signaling pathways critical for cellular functions.
- The role of MMPs in cancer extends beyond matrix degradation, involving complex signaling interactions.
Conclusions:
- MMPs possess diverse functions in development and cancer, including non-proteolytic activities.
- Understanding these multifaceted roles is crucial for developing effective MMP-based therapies.
- Novel insights into MMP functionality necessitate revisiting MMPs as drug targets for cancer and other diseases.
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