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Pharmaceuticals 2018, 11(1), 4; https://doi.org/10.3390/ph11010004

Endolysosomal Cation Channels and Cancer—A Link with Great Potential

1
Munich Center for Integrated Protein Science CIPSM, 81377 München, Germany
2
Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 München, Germany
*
Authors to whom correspondence should be addressed.
Received: 14 December 2017 / Revised: 1 January 2018 / Accepted: 4 January 2018 / Published: 5 January 2018
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Abstract

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. View Full-Text
Keywords: calcium; TPC; two-pore; lysosome; TPC1; TPC2; TRPML; mucolipin; MCOLN; mTOR; TRPML1; TFEB calcium; TPC; two-pore; lysosome; TPC1; TPC2; TRPML; mucolipin; MCOLN; mTOR; TRPML1; TFEB
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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. (CC BY 4.0).
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Grimm, C.; Bartel, K.; Vollmar, A.M.; Biel, M. Endolysosomal Cation Channels and Cancer—A Link with Great Potential. Pharmaceuticals 2018, 11, 4.

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