Membrane-type matrix metalloproteases as diverse effectors of cancer progression

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http://hdl.handle.net/10138/298089

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Turunen , S P , Tatti-Bugaeva , O & Lehti , K 2017 , ' Membrane-type matrix metalloproteases as diverse effectors of cancer progression ' , Biochimica et Biophysica Acta. Molecular Cell Research , vol. 1864 , no. 11 , pp. 1974-1988 . https://doi.org/10.1016/j.bbamcr.2017.04.002

Title: Membrane-type matrix metalloproteases as diverse effectors of cancer progression
Author: Turunen, S. Pauliina; Tatti-Bugaeva, Olga; Lehti, Kaisa
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
Date: 2017-11
Language: eng
Number of pages: 15
Belongs to series: Biochimica et Biophysica Acta. Molecular Cell Research
ISSN: 0167-4889
URI: http://hdl.handle.net/10138/298089
Abstract: Membrane-type matrix metalloproteases (MT-MMP) are pivotal regulators of cell invasion, growth and survival. Tethered to the cell membranes by a transmembrane domain or GPI-anchor, the six MT-MMPs can exert these functions via cell surface-associated extracellular matrix degradation or proteolytic protein processing, including shedding or release of signaling receptors, adhesion molecules, growth factors and other pericellular proteins. By interactions with signaling scaffold or cytoskeleton, the C-terminal cytoplasmic tail of the transmembrane MT-MMPs further extends their functionality to signaling or structural relay. MT-MMPs are differentially expressed in cancer. The most extensively studied MMP14/MT1-MMP is induced in various cancers along malignant transformation via pathways activated by mutations in tumor suppressors or proto-oncogenes and changes in tumor microenvironment including cellular heterogeneity, extracellular matrix composition, tissue oxygenation, and inflammation. Classically such induction involves transcriptional programs related to epithelial-to-mesenchymal transition. Besides inhibition by endogenous tissue inhibitors, MT-MMP activities are spatially and timely regulated at multiple levels by microtubular vesicular trafficking, dimerization/oligomerization, other interactions and localization in the actin-based invadosomes, in both tumor and the stroma. The functions of MT-MMPs are multifaceted within reciprocal cellular responses in the evolving tumor microenvironment, which poses the importance of these proteases beyond the central function as matrix scissors, and necessitates us to rethink MT-MMPs as dynamic signaling proteases of cancer. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman.
Subject: Membrane-type matrix metalloprotease
proteolysis
cancer invasion
EMT
tumor microenvironment
extracellular matrix
TUMOR-CELL INVASION
EPITHELIAL-MESENCHYMAL TRANSITION
3-DIMENSIONAL EXTRACELLULAR-MATRIX
HUMAN ENDOTHELIAL-CELLS
BREAST-CANCER
GROWTH-FACTOR
DOWN-REGULATION
HEMOPEXIN DOMAIN
CYTOPLASMIC TAIL
MT1-MMP ACTIVITY
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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