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Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis

Cancer is a leading cause of death worldwide, and its incidence is rising with numbers expected to increase 70% in the next two decades. The fact that current mainline treatments for cancer patients are accompanied by debilitating side effects prompts a growing demand for new therapies that not only...

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Autores principales: De Ieso, Michael L., Yool, Andrea J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996923/
https://www.ncbi.nlm.nih.gov/pubmed/29922644
http://dx.doi.org/10.3389/fchem.2018.00135
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author De Ieso, Michael L.
Yool, Andrea J.
author_facet De Ieso, Michael L.
Yool, Andrea J.
author_sort De Ieso, Michael L.
collection PubMed
description Cancer is a leading cause of death worldwide, and its incidence is rising with numbers expected to increase 70% in the next two decades. The fact that current mainline treatments for cancer patients are accompanied by debilitating side effects prompts a growing demand for new therapies that not only inhibit growth and proliferation of cancer cells, but also control invasion and metastasis. One class of targets gaining international attention is the aquaporins, a family of membrane-spanning water channels with diverse physiological functions and extensive tissue-specific distributions in humans. Aquaporins−1,−2,−3,−4,−5,−8, and−9 have been linked to roles in cancer invasion, and metastasis, but their mechanisms of action remain to be fully defined. Aquaporins are implicated in the metastatic cascade in processes of angiogenesis, cellular dissociation, migration, and invasion. Cancer invasion and metastasis are proposed to be potentiated by aquaporins in boosting tumor angiogenesis, enhancing cell volume regulation, regulating cell-cell and cell-matrix adhesions, interacting with actin cytoskeleton, regulating proteases and extracellular-matrix degrading molecules, contributing to the regulation of epithelial-mesenchymal transitions, and interacting with signaling pathways enabling motility and invasion. Pharmacological modulators of aquaporin channels are being identified and tested for therapeutic potential, including compounds derived from loop diuretics, metal-containing organic compounds, plant natural products, and other small molecules. Further studies on aquaporin-dependent functions in cancer metastasis are needed to define the differential contributions of different classes of aquaporin channels to regulation of fluid balance, cell volume, small solute transport, signal transduction, their possible relevance as rate limiting steps, and potential values as therapeutic targets for invasion and metastasis.
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spelling pubmed-59969232018-06-19 Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis De Ieso, Michael L. Yool, Andrea J. Front Chem Chemistry Cancer is a leading cause of death worldwide, and its incidence is rising with numbers expected to increase 70% in the next two decades. The fact that current mainline treatments for cancer patients are accompanied by debilitating side effects prompts a growing demand for new therapies that not only inhibit growth and proliferation of cancer cells, but also control invasion and metastasis. One class of targets gaining international attention is the aquaporins, a family of membrane-spanning water channels with diverse physiological functions and extensive tissue-specific distributions in humans. Aquaporins−1,−2,−3,−4,−5,−8, and−9 have been linked to roles in cancer invasion, and metastasis, but their mechanisms of action remain to be fully defined. Aquaporins are implicated in the metastatic cascade in processes of angiogenesis, cellular dissociation, migration, and invasion. Cancer invasion and metastasis are proposed to be potentiated by aquaporins in boosting tumor angiogenesis, enhancing cell volume regulation, regulating cell-cell and cell-matrix adhesions, interacting with actin cytoskeleton, regulating proteases and extracellular-matrix degrading molecules, contributing to the regulation of epithelial-mesenchymal transitions, and interacting with signaling pathways enabling motility and invasion. Pharmacological modulators of aquaporin channels are being identified and tested for therapeutic potential, including compounds derived from loop diuretics, metal-containing organic compounds, plant natural products, and other small molecules. Further studies on aquaporin-dependent functions in cancer metastasis are needed to define the differential contributions of different classes of aquaporin channels to regulation of fluid balance, cell volume, small solute transport, signal transduction, their possible relevance as rate limiting steps, and potential values as therapeutic targets for invasion and metastasis. Frontiers Media S.A. 2018-04-25 /pmc/articles/PMC5996923/ /pubmed/29922644 http://dx.doi.org/10.3389/fchem.2018.00135 Text en Copyright © 2018 De Ieso and Yool. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
De Ieso, Michael L.
Yool, Andrea J.
Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis
title Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis
title_full Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis
title_fullStr Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis
title_full_unstemmed Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis
title_short Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis
title_sort mechanisms of aquaporin-facilitated cancer invasion and metastasis
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996923/
https://www.ncbi.nlm.nih.gov/pubmed/29922644
http://dx.doi.org/10.3389/fchem.2018.00135
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