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Transient Receptor Potential (TRP) Channels: Markers and Therapeutic Targets for...
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Transient Receptor Potential (TRP) Channels: Markers and Therapeutic Targets for Cancer?

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 29200

Special Issue Editors

Dr. Maria Beatrice Morelli

E-Mail Website
Guest Editor
School of Pharmacy, University of Camerino, 62032 Camerino, Italy
Interests: glioblastoma; TRP channel; mucolipins; autophagy; overall survival; transient receptor potential channels; tumor progression; chemotherapy resistance;cancer biology; cancer stem cell; circulating tumor cell; liquid biopsy; biomarkers; ion channel; natural compound; cannabinoids
Special Issues, Collections and Topics in MDPI journals
Dr. Amantini Consuelo

E-Mail Website
Guest Editor
School of Bioscience and Biotechnology, University of Camerino, 62032 Camerino, Italy
Interests: TRP; cancer biology; apoptosis; autophagy; senescence; circulating stem cell; chemoresistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is now evident that ion channels such as the transient receptor potential (TRP) channels play a crucial role in the development and progression of cancer. Although these channels are frequently and abundantly expressed in many tumors, their expression and activity in the context of specific types of cancer is revealing many different roles to clarify. There is also the need to identify the specific TRP contribution in each phase of the cancerous process, from tumor growth, invasion, angiogenesis, and drug resistance to metastasis formation.

Hence, this Special Issue of Biomolecules is dedicated to exploring the roles of TRP in cancer. The main goal is to collect articles that describe recent progress in elucidating the mechanisms by which these channels modulate tumor progression. Despite the extensive research efforts, neoplastic diseases remain a leading cause of death and morbidity worldwide together with the rapid evolution of resistance in tumor cells to the current therapeutic opportunities. Therefore, clinical research must promote innovative strategies targeting unexplored cancer-relevant markers, such as TRP channels, which could hold promise. Several natural products, such as capsaicinoids, cannabinoids, and terpenes, have been demonstrated to be TRP channel modulators and have significantly contributed to our current knowledge on TRP biology. Therefore, we encourage scientists of diverse backgrounds to contribute original research or review articles covering studies on TRP characterization and translational approaches of clinical relevance.

Dr. Morelli Maria Beatrice
Dr. Amantini Consuelo
Guest Editors

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. Biomolecules 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 2700 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
  • cancer
  • ion channel
  • tumor progression
  • natural compound
  • calcium signaling
  • cell death
  • autophagy
  • senescence

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Published Papers (7 papers)

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Editorial

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3 pages, 169 KiB  
Editorial
Transient Receptor Potential (TRP) Channels: Markers and Therapeutic Targets for Cancer?
by Maria Beatrice Morelli and Consuelo Amantini
Biomolecules 2022, 12(4), 547; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12040547 - 06 Apr 2022
Cited by 7 | Viewed by 1282
Abstract
This Special Issue in Biomolecules explores the roles of Transient Receptor Potential channels (TRPs) in cancer [...] Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels: Markers and Therapeutic Targets for Cancer?)

Research

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14 pages, 7816 KiB  
Article
The Mucolipin TRPML2 Channel Enhances the Sensitivity of Multiple Myeloma Cell Lines to Ibrutinib and/or Bortezomib Treatment
by Giorgio Santoni, Consuelo Amantini, Federica Maggi, Oliviero Marinelli, Matteo Santoni and Maria Beatrice Morelli
Biomolecules 2022, 12(1), 107; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12010107 - 09 Jan 2022
Cited by 4 | Viewed by 1834
Abstract
Multiple myeloma (MM) is a haematological B cell malignancy characterised by clonal proliferation of plasma cells and their accumulation in the bone marrow. The aim of the present study is the evaluation of biological effects of Ibrutinib in human MM cell lines alone [...] Read more.
Multiple myeloma (MM) is a haematological B cell malignancy characterised by clonal proliferation of plasma cells and their accumulation in the bone marrow. The aim of the present study is the evaluation of biological effects of Ibrutinib in human MM cell lines alone or in combination with different doses of Bortezomib. In addition, the relationship between the expression of TRPML2 channels and chemosensitivity of different MM cell lines to Ibrutinib administered alone or in combination with Bortezomib has been evaluated. By RT-PCR and Western blot analysis, we found that the Ibrutinib-resistant U266 cells showed lower TRPML2 expression, whereas higher TRPML2 mRNA and protein levels were evidenced in RPMI cells. Moreover, TRPML2 gene silencing in RPMI cells markedly reverted the effects induced by Ibrutinib alone or in combination with Bortezomib suggesting that the sensitivity to Ibrutinib is TRPML2 mediated. In conclusion, this study suggests that the expression of TRPML2 in MM cells increases the sensitivity to Ibrutinib treatment, suggesting for a potential stratification of Ibrutinib sensitivity of MM patients on the basis of the TRPML2 expression. Furthermore, studies in vitro and in vivo should still be necessary to completely address the molecular mechanisms and the potential role of TRPML2 channels in therapy and prognosis of MM patients. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels: Markers and Therapeutic Targets for Cancer?)
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Review

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22 pages, 1672 KiB  
Review
TRP Channels as Molecular Targets to Relieve Cancer Pain
by Milena Duitama, Yurany Moreno, Sandra Paola Santander, Zulma Casas, Jhon Jairo Sutachan, Yolima P. Torres and Sonia L. Albarracín
Biomolecules 2022, 12(1), 1; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12010001 - 21 Dec 2021
Cited by 18 | Viewed by 5390
Abstract
Transient receptor potential (TRP) channels are critical receptors in the transduction of nociceptive stimuli. The microenvironment of diverse types of cancer releases substances, including growth factors, neurotransmitters, and inflammatory mediators, which modulate the activity of TRPs through the regulation of intracellular signaling pathways. [...] Read more.
Transient receptor potential (TRP) channels are critical receptors in the transduction of nociceptive stimuli. The microenvironment of diverse types of cancer releases substances, including growth factors, neurotransmitters, and inflammatory mediators, which modulate the activity of TRPs through the regulation of intracellular signaling pathways. The modulation of TRP channels is associated with the peripheral sensitization observed in patients with cancer, which results in mild noxious sensory stimuli being perceived as hyperalgesia and allodynia. Secondary metabolites derived from plant extracts can induce the activation, blocking, and desensitization of TRP channels. Thus, these compounds could act as potential therapeutic agents, as their antinociceptive properties could be beneficial in relieving cancer-derived pain. In this review, we will summarize the role of TRPV1 and TRPA1 in pain associated with cancer and discuss molecules that have been reported to modulate these channels, focusing particularly on the mechanisms of channel activation associated with molecules released in the tumor microenvironment. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels: Markers and Therapeutic Targets for Cancer?)
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9 pages, 821 KiB  
Review
Endolysosomal Cation Channels and MITF in Melanocytes and Melanoma
by Carla Abrahamian and Christian Grimm
Biomolecules 2021, 11(7), 1021; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11071021 - 13 Jul 2021
Cited by 12 | Viewed by 3879
Abstract
Microphthalmia-associated transcription factor (MITF) is the principal transcription factor regulating pivotal processes in melanoma cell development, growth, survival, proliferation, differentiation and invasion. In recent years, convincing evidence has been provided attesting key roles of endolysosomal cation channels, specifically TPCs and TRPMLs, in cancer, [...] Read more.
Microphthalmia-associated transcription factor (MITF) is the principal transcription factor regulating pivotal processes in melanoma cell development, growth, survival, proliferation, differentiation and invasion. In recent years, convincing evidence has been provided attesting key roles of endolysosomal cation channels, specifically TPCs and TRPMLs, in cancer, including breast cancer, glioblastoma, bladder cancer, hepatocellular carcinoma and melanoma. In this review, we provide a gene expression profile of these channels in different types of cancers and decipher their roles, in particular the roles of two-pore channel 2 (TPC2) and TRPML1 in melanocytes and melanoma. We specifically discuss the signaling cascades regulating MITF and the relationship between endolysosomal cation channels, MAPK, canonical Wnt/GSK3 pathways and MITF. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels: Markers and Therapeutic Targets for Cancer?)
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23 pages, 723 KiB  
Review
TRPV Protein Family—From Mechanosensing to Cancer Invasion
by Tytti Kärki and Sari Tojkander
Biomolecules 2021, 11(7), 1019; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11071019 - 13 Jul 2021
Cited by 34 | Viewed by 6902
Abstract
Biophysical cues from the cellular microenvironment are detected by mechanosensitive machineries that translate physical signals into biochemical signaling cascades. At the crossroads of extracellular space and cell interior are located several ion channel families, including TRP family proteins, that are triggered by mechanical [...] Read more.
Biophysical cues from the cellular microenvironment are detected by mechanosensitive machineries that translate physical signals into biochemical signaling cascades. At the crossroads of extracellular space and cell interior are located several ion channel families, including TRP family proteins, that are triggered by mechanical stimuli and drive intracellular signaling pathways through spatio-temporally controlled Ca2+-influx. Mechanosensitive Ca2+-channels, therefore, act as critical components in the rapid transmission of physical signals into biologically compatible information to impact crucial processes during development, morphogenesis and regeneration. Given the mechanosensitive nature of many of the TRP family channels, they must also respond to the biophysical changes along the development of several pathophysiological conditions and have also been linked to cancer progression. In this review, we will focus on the TRPV, vanilloid family of TRP proteins, and their connection to cancer progression through their mechanosensitive nature. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels: Markers and Therapeutic Targets for Cancer?)
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17 pages, 1325 KiB  
Review
Transient Receptor Potential (TRP) Channels in Haematological Malignancies: An Update
by Federica Maggi, Maria Beatrice Morelli, Massimo Nabissi, Oliviero Marinelli, Laura Zeppa, Cristina Aguzzi, Giorgio Santoni and Consuelo Amantini
Biomolecules 2021, 11(5), 765; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11050765 - 20 May 2021
Cited by 7 | Viewed by 3258
Abstract
Transient receptor potential (TRP) channels are improving their importance in different cancers, becoming suitable as promising candidates for precision medicine. Their important contribution in calcium trafficking inside and outside cells is coming to light from many papers published so far. Encouraging results on [...] Read more.
Transient receptor potential (TRP) channels are improving their importance in different cancers, becoming suitable as promising candidates for precision medicine. Their important contribution in calcium trafficking inside and outside cells is coming to light from many papers published so far. Encouraging results on the correlation between TRP and overall survival (OS) and progression-free survival (PFS) in cancer patients are available, and there are as many promising data from in vitro studies. For what concerns haematological malignancy, the role of TRPs is still not elucidated, and data regarding TRP channel expression have demonstrated great variability throughout blood cancer so far. Thus, the aim of this review is to highlight the most recent findings on TRP channels in leukaemia and lymphoma, demonstrating their important contribution in the perspective of personalised therapies. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels: Markers and Therapeutic Targets for Cancer?)
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14 pages, 808 KiB  
Review
TRPM4 in Cancer—A New Potential Drug Target
by Anna Borgström, Christine Peinelt and Paulina Stokłosa
Biomolecules 2021, 11(2), 229; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11020229 - 05 Feb 2021
Cited by 26 | Viewed by 5622
Abstract
Transient receptor potential melastatin 4 (TRPM4) is widely expressed in various organs and associated with cardiovascular and immune diseases. Lately, the interest in studies on TRPM4 in cancer has increased. Thus far, TRPM4 has been investigated in diffuse large B-cell lymphoma, prostate, colorectal, [...] Read more.
Transient receptor potential melastatin 4 (TRPM4) is widely expressed in various organs and associated with cardiovascular and immune diseases. Lately, the interest in studies on TRPM4 in cancer has increased. Thus far, TRPM4 has been investigated in diffuse large B-cell lymphoma, prostate, colorectal, liver, breast, urinary bladder, cervical, and endometrial cancer. In several types of cancer TRPM4 is overexpressed and contributes to cancer hallmark functions such as increased proliferation and migration and cell cycle shift. Hence, TRPM4 is a potential prognostic cancer marker and a promising anticancer drug target candidate. Currently, the underlying mechanism by which TRPM4 contributes to cancer hallmark functions is under investigation. TRPM4 is a Ca2+-activated monovalent cation channel, and its ion conductivity can decrease intracellular Ca2+ signaling. Furthermore, TRPM4 can interact with different partner proteins. However, the lack of potent and specific TRPM4 inhibitors has delayed the investigations of TRPM4. In this review, we summarize the potential mechanisms of action and discuss new small molecule TRPM4 inhibitors, as well as the TRPM4 antibody, M4P. Additionally, we provide an overview of TRPM4 in human cancer and discuss TRPM4 as a diagnostic marker and anticancer drug target. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels: Markers and Therapeutic Targets for Cancer?)
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