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Calcium Channel Regulation in Cancer: Unravelling the Molecular Mechanisms beneath the Membrane

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

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 9589

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Special Issue Editor

Dr. Dimitra Gkika

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Guest Editor

CANcer Heterogeneity, Plasticity and Resistance to THERapies Lab, Faculty of Sciences and Technologies, University of Lille, 59000 Lille, France
Interests: ion channel; TRP channel; calcium homeostasis; cancer; angiogenesis; small GTPases; androgen receptor; steroid fast non genomic actions; expression profile; cell migration; cell adhesion

Special Issue Information

Dear Colleagues,

Over the last decades, an increasing number of calcium channels located at the cell surface or inner membranes, including voltage-dependent calcium channels (VDCC), transient receptor potential (TRP), store-operated calcium (SOC) channels, the inositol 1,4,5-trisphosphate receptor (IP3R), and mitochondrial calcium uniporter (MCU), have been suggested as clinical markers and/or therapeutical targets for cancer. In this perspective, major advances have contributed to a deeper understanding of the regulatory mechanisms controlling the channel activity, as well as its consequences in tumour initiation, growth, and metastasis.

I therefore would like to invite you to participate in this Special Issue, "Calcium Channel Regulation in Cancer: Unravelling the Molecular Mechanisms beneath the Membrane", by presenting your most recent research or ideas about intracellular factors such as channel associated factors, kinases, partner proteins, small GTPases, calcium binding proteins, signalling molecules affecting channel functioning, and the consequential major aspects of carcinogenesis.

Assoc. Prof. Dimitra Gkika
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

ion channel
calcium signalling
partner protein
protein–protein interaction
TRP channel
channel subunit
TRP
ORAI
CaV
IP3R
MCU
cancer
tumour initiation
tumour growth
metastasis

Published Papers (3 papers)

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Research

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20 pages, 4497 KiB

Open AccessArticle

Involvement of ORAI1/SOCE in Human AML Cell Lines and Primary Cells According to ABCB1 Activity, LSC Compartment and Potential Resistance to Ara-C Exposure

by Clara Lewuillon, Aurélie Guillemette, Sofia Titah, Faruk Azam Shaik, Nathalie Jouy, Ossama Labiad, Valerio Farfariello, Marie-Océane Laguillaumie, Thierry Idziorek, Adeline Barthélémy, Pauline Peyrouze, Céline Berthon, Mehmet Cagatay Tarhan, Meyling Cheok, Bruno Quesnel, Loïc Lemonnier and Yasmine Touil

Int. J. Mol. Sci. 2022, 23(10), 5555; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105555 - 16 May 2022

Cited by 4 | Viewed by 2570

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy with a high risk of relapse. This issue is associated with the development of mechanisms leading to drug resistance that are not yet fully understood. In this context, we previously showed the clinical significance of the ATP binding cassette subfamily B-member 1 (ABCB1) in AML patients, namely its association with stemness markers and an overall worth prognosis. Calcium signaling dysregulations affect numerous cellular functions and are associated with the development of the hallmarks of cancer. However, in AML, calcium-dependent signaling pathways remain poorly investigated. With this study, we show the involvement of the ORAI1 calcium channel in store-operated calcium entry (SOCE), the main calcium entry pathway in non-excitable cells, in two representative human AML cell lines (KG1 and U937) and in primary cells isolated from patients. Moreover, our data suggest that in these models, SOCE varies according to the differentiation status, ABCB1 activity level and leukemic stem cell (LSC) proportion. Finally, we present evidence that ORAI1 expression and SOCE amplitude are modulated during the establishment of an apoptosis resistance phenotype elicited by the chemotherapeutic drug Ara-C. Our results therefore suggest ORAI1/SOCE as potential markers of AML progression and drug resistance apparition. Full article

(This article belongs to the Special Issue Calcium Channel Regulation in Cancer: Unravelling the Molecular Mechanisms beneath the Membrane)

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16 pages, 23844 KiB

Open AccessArticle

Developing a Mathematical Model of Intracellular Calcium Dynamics for Evaluating Combined Anticancer Effects of Afatinib and RP4010 in Esophageal Cancer

by Yan Chang, Marah Funk, Souvik Roy, Elizabeth Stephenson, Sangyong Choi, Hristo V. Kojouharov, Benito Chen and Zui Pan

Int. J. Mol. Sci. 2022, 23(3), 1763; https://doi.org/10.3390/ijms23031763 - 03 Feb 2022

Cited by 11 | Viewed by 2418

Abstract

Targeting dysregulated Ca²⁺ signaling in cancer cells is an emerging chemotherapy approach. We previously reported that store-operated Ca²⁺ entry (SOCE) blockers, such as RP4010, are promising antitumor drugs for esophageal cancer. As a tyrosine kinase inhibitor (TKI), afatinib received FDA approval to be used in targeted therapy for patients with EGFR mutation-positive cancers. While preclinical studies and clinical trials have shown that afatinib has benefits for esophageal cancer patients, it is not known whether a combination of afatinib and RP4010 could achieve better anticancer effects. Since TKI can alter intracellular Ca²⁺ dynamics through EGFR/phospholipase C-γ pathway, in this study, we evaluated the inhibitory effect of afatinib and RP4010 on intracellular Ca²⁺ oscillations in KYSE-150, a human esophageal squamous cell carcinoma cell line, using both experimental and mathematical simulations. Our mathematical simulation of Ca²⁺ oscillations could fit well with experimental data responding to afatinib or RP4010, both separately or in combination. Guided by simulation, we were able to identify a proper ratio of afatinib and RP4010 for combined treatment, and such a combination presented synergistic anticancer-effect evidence by experimental measurement of intracellular Ca²⁺ and cell proliferation. This intracellular Ca²⁺ dynamic-based mathematical simulation approach could be useful for a rapid and cost-effective evaluation of combined targeting therapy drugs. Full article

(This article belongs to the Special Issue Calcium Channel Regulation in Cancer: Unravelling the Molecular Mechanisms beneath the Membrane)

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Review

Jump to: Research

11 pages, 1184 KiB

Open AccessReview

Role of Orai3 in the Pathophysiology of Cancer

by Jose Sanchez-Collado, Isaac Jardin, Jose J. López, Victor Ronco, Gines M. Salido, Charlotte Dubois, Natalia Prevarskaya and Juan A. Rosado

Int. J. Mol. Sci. 2021, 22(21), 11426; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111426 - 22 Oct 2021

Cited by 10 | Viewed by 3756

Abstract

The mammalian exclusive Orai3 channel participates in the generation and/or modulation of two independent Ca²⁺ currents, the store-operated current, I_crac, involving functional interactions between the stromal interaction molecules (STIM), STIM1/STIM2, and Orai1/Orai2/Orai3, as well as the store-independent arachidonic acid (AA) (or leukotriene C4)-regulated current I_a_rc, which involves Orai1, Orai3 and STIM1. Overexpression of functional Orai3 has been described in different neoplastic cells and cancer tissue samples as compared to non-tumor cells or normal adjacent tissue. In these cells, Orai3 exhibits a cell-specific relevance in Ca²⁺ influx. In estrogen receptor-positive breast cancer cells and non-small cell lung cancer (NSCLC) cells store-operated Ca²⁺ entry (SOCE) is strongly dependent on Orai3 expression while in colorectal cancer and pancreatic adenocarcinoma cells Orai3 predominantly modulates SOCE. On the other hand, in prostate cancer cells Orai3 expression has been associated with the formation of Orai1/Orai3 heteromeric channels regulated by AA and reduction in SOCE, thus leading to enhanced proliferation. Orai3 overexpression is associated with supporting several cancer hallmarks, including cell cycle progression, proliferation, migration, and apoptosis resistance. This review summarizes the current knowledge concerning the functional role of Orai3 in the pathogenesis of cancer. Full article

(This article belongs to the Special Issue Calcium Channel Regulation in Cancer: Unravelling the Molecular Mechanisms beneath the Membrane)

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