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TRP Channels in Cancer: New Avenues for Diagnosis, Prognostication, and Therapy

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 7784

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Special Issue Editor

Dr. Arpad Szallasi

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Guest Editor

Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary
Interests: the capsaicin receptor TRPV1; small molecule TRP inhibitors; TRP channels and cancer; neurogenic inflammation and cancer; cancer pain
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Transient Receptor Potential (TRP) channels are multifunctional signaling molecules, with important roles in cell growth and differentiation. Several TRP channels show altered expression in cancers, though it is unclear if this is cause or consequence of the disease.

Regardless of the underlying pathology, this altered expression can be used for cancer diagnosis and prognostication. Furthermore, such altered TRP channel expression may constitute a novel therapeutic target. For example, high-dose capsaicin (the paradigmal TRPV1 agonist) administration can kill cancer cells owing to the Ca²⁺ overload that it causes. This observation implies that cancers that overexpress TRP channels may represent promising indications for drugs that target these proteins. To deliver such drugs without causing unacceptable side-effects is a challenge, but cancers that are amenable to topical therapy are viable targets.

This Special Issue will explore the current state of this rapidly evolving field, from the role of TRP channels in malignant transformation, cancer growth and metastasis, through the use of altered TRP channel expression in cancer diagnosis and prognostication, to targeting TRP channels to kill cancer cells or relieve cancer pain. Experimental studies with tumor cell lines and/or animal models of human cancer, critical review articles of old concepts and new thoughts are all welcome for consideration.

Dr. Arpad Szallasi
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
TRPs in tumor promotion
TRPs in malignant transformation
metastasis and neurogenic inflammation
altered TRP expression in cancer diagnosis
TRP expression in prognostication
TRPs as oncotargets

Published Papers (6 papers)

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Research

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13 pages, 7794 KiB

Open AccessArticle

Transient Receptor Potential Ankyrin 1 Ion Channel Is Expressed in Osteosarcoma and Its Activation Reduces Viability

by Lina Hudhud, Katalin Rozmer, Angéla Kecskés, Krisztina Pohóczky, Noémi Bencze, Krisztina Buzás, Éva Szőke and Zsuzsanna Helyes

Int. J. Mol. Sci. 2024, 25(7), 3760; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25073760 - 28 Mar 2024

Viewed by 416

Abstract

Osteosarcoma is a highly malignant, painful cancer with poor treatment opportunities and a bad prognosis. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are non-selective cation channels that have been of great interest in cancer, as their expression is increased in some malignancies. In our study we aim to characterize the expression and functionality of the TRPA1 and TRPV1 channels in human and mouse osteosarcoma tissues and in a mouse cell line. TRPA1/Trpa1 and TRPV1/Trpv1 mRNA expressions were demonstrated by PCR gel electrophoresis and RNAscope in situ hybridization. The function of these channels was confirmed by their radioactive ₄₅Ca²⁺ uptake in response to the TRPA1 agonist, Allyl-isothiocyanate (AITC), and TRPV1 agonist, capsaicin, in K7M2 cells. An ATP-based K2M7 cell viability luminescence assay was used to determine cell viability after AITC or capsaicin treatments. Both TRPA1/Trpa1 and TRPV1/Trpv1 were expressed similarly in human and mouse osteosarcoma tissues, while Trpa1 transcripts were more abundantly present in K7M2 cells. TRPA1 activation with 200 µM AITC induced a significant ₄₅Ca²⁺ influx into K7M2 cells, and the antagonist attenuated this effect. In accordance with the lower Trpv1 expression, capsaicin induced a moderate ₄₅Ca²⁺ uptake, which did not reach the level of statistical significance. Both AITC and capsaicin significantly reduced K7M2 cell viability, demonstrating EC₅₀ values of 22 µM and 74 µM. The viability-decreasing effect of AITC was significantly but only partially antagonized by HC-030031, but the action of capsaicin was not affected by the TRPV1 antagonist capsazepine. We provide here the first data on the functional expression of the TRPA1 and TRPV1 ion channels in osteosarcoma, suggesting novel diagnostic and/or therapeutic perspectives. Full article

(This article belongs to the Special Issue TRP Channels in Cancer: New Avenues for Diagnosis, Prognostication, and Therapy)

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18 pages, 4479 KiB

Open AccessArticle

The Cytoplasmic Region of SARAF Reduces Triple-Negative Breast Cancer Metastasis through the Regulation of Store-Operated Calcium Entry

by María Paz Saldías, Pablo Cruz, Ian Silva, Octavio Orellana-Serradell, Boris Lavanderos, Diego Maureira, Raquel Pinto and Oscar Cerda

Int. J. Mol. Sci. 2023, 24(6), 5306; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24065306 - 10 Mar 2023

Viewed by 1497

Abstract

Triple-negative breast cancer has a poor prognosis and is non-responsive to first-line therapies; hence, new therapeutic strategies are needed. Enhanced store-operated Ca²⁺ entry (SOCE) has been widely described as a contributing factor to tumorigenic behavior in several tumor types, particularly in breast cancer cells. SOCE-associated regulatory factor (SARAF) acts as an inhibitor of the SOCE response and, therefore, can be a potential antitumor factor. Herein, we generated a C-terminal SARAF fragment to evaluate the effect of overexpression of this peptide on the malignancy of triple-negative breast cancer cell lines. Using both in vitro and in vivo approaches, we showed that overexpression of the C-terminal SARAF fragment reduced proliferation, cell migration, and the invasion of murine and human breast cancer cells by decreasing the SOCE response. Our data suggest that regulating the activity of the SOCE response via SARAF activity might constitute the basis for further alternative therapeutic strategies for triple-negative breast cancer. Full article

(This article belongs to the Special Issue TRP Channels in Cancer: New Avenues for Diagnosis, Prognostication, and Therapy)

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10 pages, 2889 KiB

Open AccessArticle

Expression of pH-Sensitive TRPC4 in Common Skin Tumors

by Bernadett Kurz, Hannah Philine Michael, Antonia Förch, Susanne Wallner, Florian Zeman, Sonja-Maria Decking, Ines Ugele, Constantin Hintschich, Frank Haubner, Tobias Ettl, Kathrin Renner, Christoph Brochhausen and Stephan Schreml

Int. J. Mol. Sci. 2023, 24(2), 1037; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021037 - 05 Jan 2023

Cited by 3 | Viewed by 1246

Abstract

TRPCs (transient receptor potential classical or cation channels) play a crucial role in tumor biology, especially in the Ca²⁺ homeostasis in cancer cells. TRPC4 is a pH-sensitive member of this family of proteins. As solid tumors exhibit an inversed pH-gradient with lowered extracellular and increased intracellular pH, both contributing to tumor progression, TRPC4 might be a signaling molecule in the altered tumor microenvironment. This is the first study to investigate the expression profiles of TRPC4 in common skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM) and nevus cell nevi (NCN). We found that all SCCs, NCNs, and MMs show positive TRPC4-expression, while BCCs do only in about half of the analyzed samples. These data render TRPC4 an immunohistochemical marker to distinguish SCC and BCC, and this also gives rise to future studies investigating the role of TRPC4 in tumor progression, and especially metastasis as BCCs very rarely spread and are mostly negative for TRPC4. Full article

(This article belongs to the Special Issue TRP Channels in Cancer: New Avenues for Diagnosis, Prognostication, and Therapy)

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Review

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31 pages, 1410 KiB

Open AccessReview

The Role of TRPM7 in Oncogenesis

by László Köles, Polett Ribiczey, Andrea Szebeni, Kristóf Kádár, Tibor Zelles and Ákos Zsembery

Int. J. Mol. Sci. 2024, 25(2), 719; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25020719 - 05 Jan 2024

Viewed by 1406

Abstract

This review summarizes the current understanding of the role of transient receptor potential melastatin-subfamily member 7 (TRPM7) channels in the pathophysiology of neoplastic diseases. The TRPM family represents the largest and most diverse group in the TRP superfamily. Its subtypes are expressed in virtually all human organs playing a central role in (patho)physiological events. The TRPM7 protein (along with TRPM2 and TRPM6) is unique in that it has kinase activity in addition to the channel function. Numerous studies demonstrate the role of TRPM7 chanzyme in tumorigenesis and in other tumor hallmarks such as proliferation, migration, invasion and metastasis. Here we provide an up-to-date overview about the possible role of TRMP7 in a broad range of malignancies such as tumors of the nervous system, head and neck cancers, malignant neoplasms of the upper gastrointestinal tract, colorectal carcinoma, lung cancer, neoplasms of the urinary system, breast cancer, malignant tumors of the female reproductive organs, prostate cancer and other neoplastic pathologies. Experimental data show that the increased expression and/or function of TRPM7 are observed in most malignant tumor types. Thus, TRPM7 chanzyme may be a promising target in tumor therapy. Full article

(This article belongs to the Special Issue TRP Channels in Cancer: New Avenues for Diagnosis, Prognostication, and Therapy)

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13 pages, 289 KiB

Open AccessReview

TRPM2 Channels: A Potential Therapeutic Target in Melanoma?

by Hattie M. Foster, McKenzie N. Carle, Lukas R. Jira and David W. Koh

Int. J. Mol. Sci. 2023, 24(13), 10437; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241310437 - 21 Jun 2023

Viewed by 968

Abstract

The transient receptor potential, the melastatin (TRPM) subfamily, which consists of eight known members, appears to have significant importance in melanoma progression, treatment, and prognosis. As several members were originally cloned from cancerous tissue, initial studies aimed towards identifying TRPM involvement in cancer progression and tumorigenesis. For relevance in skin cancer, previous research has shown roles for several TRPM members in skin cancer progression, growth, and patient prognosis. One unique member, TRPM2, appears to have notable therapeutic potential in the treatment of melanoma. Previous and recent studies have demonstrated increased TRPM2 expression levels in melanoma, as well as important roles for TRPM2 in melanoma growth, proliferation, and survival. TRPM2 is thus an emerging target in the treatment of melanoma, where TRPM2 antagonism may offer an additional treatment option for melanoma patients in the future. Full article

(This article belongs to the Special Issue TRP Channels in Cancer: New Avenues for Diagnosis, Prognostication, and Therapy)

30 pages, 7929 KiB

Open AccessReview

“ThermoTRP” Channel Expression in Cancers: Implications for Diagnosis and Prognosis (Practical Approach by a Pathologist)

by Arpad Szallasi

Int. J. Mol. Sci. 2023, 24(10), 9098; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24109098 - 22 May 2023

Cited by 2 | Viewed by 1648

Abstract

Temperature-sensitive transient receptor potential (TRP) channels (so-called “thermoTRPs”) are multifunctional signaling molecules with important roles in cell growth and differentiation. Several “thermoTRP” channels show altered expression in cancers, though it is unclear if this is a cause or consequence of the disease. Regardless of the underlying pathology, this altered expression may potentially be used for cancer diagnosis and prognostication. “ThermoTRP” expression may distinguish between benign and malignant lesions. For example, TRPV1 is expressed in benign gastric mucosa, but is absent in gastric adenocarcinoma. TRPV1 is also expressed both in normal urothelia and non-invasive papillary urothelial carcinoma, but no TRPV1 expression has been seen in invasive urothelial carcinoma. “ThermoTRP” expression can also be used to predict clinical outcomes. For instance, in prostate cancer, TRPM8 expression predicts aggressive behavior with early metastatic disease. Furthermore, TRPV1 expression can dissect a subset of pulmonary adenocarcinoma patients with bad prognosis and resistance to a number of commonly used chemotherapeutic agents. This review will explore the current state of this rapidly evolving field with special emphasis on immunostains that can already be added to the armoire of diagnostic pathologists. Full article

(This article belongs to the Special Issue TRP Channels in Cancer: New Avenues for Diagnosis, Prognostication, and Therapy)

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