Review
Version 1
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Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu
Version 1
: Received: 20 June 2022 / Approved: 22 June 2022 / Online: 22 June 2022 (05:19:01 CEST)
A peer-reviewed article of this Preprint also exists.
Maybee, D.V.; Ink, N.L.; Ali, M.A.M. Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu. Int. J. Mol. Sci. 2022, 23, 9513. Maybee, D.V.; Ink, N.L.; Ali, M.A.M. Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu. Int. J. Mol. Sci. 2022, 23, 9513.
Abstract
Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Recently, more research has been conducted on investigating novel subcellular localizations of MMPs and their intracellular roles at the respective locations. In this review article, we focus on the subcellular localization and novel intracellular roles of two MMPs closely related: membrane-type-1 matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase-2 (MMP-2). Although MT1-MMP is commonly known to localize on the cell surface, the protease also localizes to the cytoplasm, caveolae, Golgi, cytoskeleton, centrosome, and nucleus. At these subcellular locations, MT1-MMP functions in cell migration, macrophage metabolism, invadopodia development, spindle formation and genes expression, respectively. Similar to MT1-MMP, MMP-2 localizes to the caveolae, mitochondria, cytoskeleton, nucleus and nucleolus, and functions in calcium regulation, contractile dysfunction, genes expression and ribosomal RNA transcription. Our particular interest lies in the role MMP-2 and MT1-MMP serve within the nucleus, as it may provide critical insights into cancer epigenetics and tumor migration and invasion. We suggest that targeting nuclear MT1-MMP or MMP-2 to reduce or halt cell proliferation and migration may lead to the development of new therapies in cancer and other diseases.
Keywords
Matrix metalloproteinases (MMPs); MMP-2; MT1-MMP; intracellular roles; subcellular localization
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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