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Endolysosomal Cation Channels and Cancer—A Link with Great Potential

The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell mot...

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Autores principales: Grimm, Christian, Bartel, Karin, Vollmar, Angelika M., Biel, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874700/
https://www.ncbi.nlm.nih.gov/pubmed/29303993
http://dx.doi.org/10.3390/ph11010004
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author Grimm, Christian
Bartel, Karin
Vollmar, Angelika M.
Biel, Martin
author_facet Grimm, Christian
Bartel, Karin
Vollmar, Angelika M.
Biel, Martin
author_sort Grimm, Christian
collection PubMed
description The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism. The function of endolysosomes is critically dependent on both soluble and endolysosomal membrane proteins such as ion channels and transporters. Cation channels found in the ES include members of the TRP (transient receptor potential) channel superfamily, namely TRPML channels (mucolipins) as well as two-pore channels (TPCs). In recent studies, these channels have been found to play crucial roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or loss of these channel proteins can impact multiple endolysosomal trafficking pathways. A role for TPCs in cancer cell migration and metastasis, linked to distinct defects in endolysosomal trafficking such as integrin trafficking, has been recently established. In this review, we give an overview on the function of lysosomes in cancer with a particular focus on the roles which TPCs and TRPML channels play in the ES and how this can affect cancer cells.
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spelling pubmed-58747002018-04-02 Endolysosomal Cation Channels and Cancer—A Link with Great Potential Grimm, Christian Bartel, Karin Vollmar, Angelika M. Biel, Martin Pharmaceuticals (Basel) Review The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism. The function of endolysosomes is critically dependent on both soluble and endolysosomal membrane proteins such as ion channels and transporters. Cation channels found in the ES include members of the TRP (transient receptor potential) channel superfamily, namely TRPML channels (mucolipins) as well as two-pore channels (TPCs). In recent studies, these channels have been found to play crucial roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or loss of these channel proteins can impact multiple endolysosomal trafficking pathways. A role for TPCs in cancer cell migration and metastasis, linked to distinct defects in endolysosomal trafficking such as integrin trafficking, has been recently established. In this review, we give an overview on the function of lysosomes in cancer with a particular focus on the roles which TPCs and TRPML channels play in the ES and how this can affect cancer cells. MDPI 2018-01-05 /pmc/articles/PMC5874700/ /pubmed/29303993 http://dx.doi.org/10.3390/ph11010004 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Grimm, Christian
Bartel, Karin
Vollmar, Angelika M.
Biel, Martin
Endolysosomal Cation Channels and Cancer—A Link with Great Potential
title Endolysosomal Cation Channels and Cancer—A Link with Great Potential
title_full Endolysosomal Cation Channels and Cancer—A Link with Great Potential
title_fullStr Endolysosomal Cation Channels and Cancer—A Link with Great Potential
title_full_unstemmed Endolysosomal Cation Channels and Cancer—A Link with Great Potential
title_short Endolysosomal Cation Channels and Cancer—A Link with Great Potential
title_sort endolysosomal cation channels and cancer—a link with great potential
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874700/
https://www.ncbi.nlm.nih.gov/pubmed/29303993
http://dx.doi.org/10.3390/ph11010004
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