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Transient Receptor Potential Ion Channels as Targets in Anti-Cancer Therapies

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A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (15 April 2018) | Viewed by 24456

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Special Issue Editor

Prof. Dr. Thomas Gudermann

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Guest Editor

Ludwig-Maximilians-Universität München, Walther-Straub-Institut für Pharmakologie und Toxikologie, Goethestraße 33, 80336 München, Germany
Interests: Calcium signalling; G-protein-coupled receptors; TRP ion channels; cell proliferation

Special Issue Information

Dear Colleagues,

Over the past 10–15 years, transient receptor potential (TRP) cation channels have gained broad recognition as versatile cellular sensors and effectors. Twenty-seven functional Trp genes have been identified in the human genome, amounting to 12% of known genes coding for the pore-forming subunits of plasma membrane ion channels. Over the last few years, the new concept that TRP proteins control an exceptionally broad spectrum of salient cell functions including cell proliferation and migration has emerged. Therefore, it does not come as a surprise that changes in the expression level or function of TRP proteins have been observed in various malignancies and TRP channels are increasingly discussed as potential therapeutic targets in novel anti-cancer strategies. To review more than a decade of remarkable progress in our understanding of the contribution of TRP channels to cell proliferation, migration and tumorigenesis, the journal Pharmaceuticals now invites both reviews and original articles shedding light on TRP proteins as targets in anti-cancer therapies. The collection of manuscripts will be published as a Special Issue of the journal.

For reference, please refer to:

http://www.en.wsi.med.uni-muenchen.de/personen/professors/gudermann/publikationen/index.html

Prof. Dr. Thomas Gudermann
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

TRP channels
cell proliferation
cell migration
cytoskeleton
cancer pain
metastasis
cancer
TRP channel ligands

Related Special Issues

Transient Receptor Potential (TRP) Channels in Drug Discovery: Unlocking the Potential in Pharmaceuticals (9 articles)
Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts in Pharmaceuticals (16 articles)

Published Papers (4 papers)

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Review

10 pages, 581 KiB

Open AccessReview

Role of Chemosensory TRP Channels in Lung Cancer

by Thomas R. H. Büch, Eva A. M. Büch, Ingrid Boekhoff, Dirk Steinritz and Achim Aigner

Pharmaceuticals 2018, 11(4), 90; https://0-doi-org.brum.beds.ac.uk/10.3390/ph11040090 - 21 Sep 2018

Cited by 12 | Viewed by 3794

Abstract

Transient receptor potential (TRP) channels represent a large family of cation channels and many members of the TRP family have been shown to act as polymodal receptor molecules for irritative or potentially harmful substances. These chemosensory TRP channels have been extensively characterized in primary sensory and neuronal cells. However, in recent years the functional expression of these proteins in non-neuronal cells, e.g., in the epithelial lining of the respiratory tract has been confirmed. Notably, these proteins have also been described in a number of cancer types. As sensor molecules for noxious compounds, chemosensory TRP channels are involved in cell defense mechanisms and influence cell survival following exposure to toxic substances via the modulation of apoptotic signaling. Of note, a number of cytostatic drugs or drug metabolites can activate these TRP channels, which could affect the therapeutic efficacy of these cytostatics. Moreover, toxic inhalational substances with potential involvement in lung carcinogenesis are well established TRP activators. In this review, we present a synopsis of data on the expression of chemosensory TRP channels in lung cancer cells and describe TRP agonists and TRP-dependent signaling pathways with potential relevance to tumor biology. Furthermore, we discuss a possible role of TRP channels in the non-genomic, tumor-promoting effects of inhalational carcinogens such as cigarette smoke. Full article

(This article belongs to the Special Issue Transient Receptor Potential Ion Channels as Targets in Anti-Cancer Therapies)

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14 pages, 1209 KiB

Open AccessReview

TRPM Family Channels in Cancer

by Aline Hantute-Ghesquier, Aurélien Haustrate, Natalia Prevarskaya and V’yacheslav Lehen’kyi

Pharmaceuticals 2018, 11(2), 58; https://0-doi-org.brum.beds.ac.uk/10.3390/ph11020058 - 07 Jun 2018

Cited by 76 | Viewed by 6276

Abstract

Members of the TRPM (“Melastatin”) family fall into the subclass of the TRP channels having varying permeability to Ca²⁺ and Mg²⁺, with three members of the TRPM family being chanzymes, which contain C-terminal enzyme domains. The role of different TRPM members has been shown in various cancers such as prostate cancer for mostly TRPM8 and TRPM2, breast cancer for mostly TRPM2 and TRPM7, and pancreatic cancer for TRPM2/7/8 channels. The role of TRPM5 channels has been shown in lung cancer, TRPM1 in melanoma, and TRPM4 channel in prostate cancer as well. Thus, the TRPM family of channels may represent an appealing target for the anticancer therapy. Full article

(This article belongs to the Special Issue Transient Receptor Potential Ion Channels as Targets in Anti-Cancer Therapies)

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Graphical abstract

25 pages, 2541 KiB

Open AccessReview

The Role of TRP Channels in the Metastatic Cascade

by Benedikt Fels, Etmar Bulk, Zoltán Pethő and Albrecht Schwab

Pharmaceuticals 2018, 11(2), 48; https://0-doi-org.brum.beds.ac.uk/10.3390/ph11020048 - 17 May 2018

Cited by 60 | Viewed by 6968

Abstract

A dysregulated cellular Ca²⁺ homeostasis is involved in multiple pathologies including cancer. Changes in Ca²⁺ signaling caused by altered fluxes through ion channels and transporters (the transportome) are involved in all steps of the metastatic cascade. Cancer cells thereby “re-program” and “misuse” the cellular transportome to regulate proliferation, apoptosis, metabolism, growth factor signaling, migration and invasion. Cancer cells use their transportome to cope with diverse environmental challenges during the metastatic cascade, like hypoxic, acidic and mechanical cues. Hence, ion channels and transporters are key modulators of cancer progression. This review focuses on the role of transient receptor potential (TRP) channels in the metastatic cascade. After briefly introducing the role of the transportome in cancer, we discuss TRP channel functions in cancer cell migration. We highlight the role of TRP channels in sensing and transmitting cues from the tumor microenvironment and discuss their role in cancer cell invasion. We identify open questions concerning the role of TRP channels in circulating tumor cells and in the processes of intra- and extravasation of tumor cells. We emphasize the importance of TRP channels in different steps of cancer metastasis and propose cancer-specific TRP channel blockade as a therapeutic option in cancer treatment. Full article

(This article belongs to the Special Issue Transient Receptor Potential Ion Channels as Targets in Anti-Cancer Therapies)

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8 pages, 764 KiB

Open AccessFeature PaperReview

Endolysosomal Cation Channels and Cancer—A Link with Great Potential

by Christian Grimm, Karin Bartel, Angelika M. Vollmar and Martin Biel

Pharmaceuticals 2018, 11(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/ph11010004 - 05 Jan 2018

Cited by 44 | Viewed by 6943

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. Full article

(This article belongs to the Special Issue Transient Receptor Potential Ion Channels as Targets in Anti-Cancer Therapies)

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