Submit to Biomedicines Review for Biomedicines Propose a Special Issue

Journal Browser

Calcium Signaling and Its Dysregulation in Cancer

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 14859

Share This Special Issue

Special Issue Editor

Dr. Randolph C. Elble

E-Mail Website
Guest Editor

Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
Interests: epithelial differentiation processes in breast, oral, and lung cancers; metastasis mechanisms; cell junctional signaling; EGFR, Her2, and E-cadherin in anoikis; role of intracellular calcium stores in proliferation, differentiation, and cell death; p53, cell stress, and DNA damage response; cell senescence; CLCA gene family
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There is a growing appreciation of the role that intracellular calcium plays in both tumor suppression and progression. Calcium is the common currency of differentiation and homeostasis. It is stored primarily in the endoplasmic reticulum, rationed according to need, and replenished from the extracellular milieu via store-operated calcium entry (SOCE). This currency is disbursed by the inositol triphosphate (IP3) receptor in response to diverse extracellular signals. The rate of release is governed by regulators of metabolism and proliferation, differentiation, autophagy, survival, and programmed cell death, with different outcomes depending on the strength of the signal and context. This system is fundamentally tumor-suppressive, and cancer cells must find ways to subvert it in order to exploit its growth-promoting effects.

This Special Issue invites both original manuscripts describing novel findings and cutting-edge review articles illustrating the many mechanisms by which cancer cells dysregulate SOCE, IP3 and ryanodine receptors, calcium transfer to mitochondria, and signaling to downstream effectors and targets to prevent cell death and enhance metabolism, mitogenesis, and metastasis.

Prof. Dr. Randolph C. Elble
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. Biomedicines 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 2600 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

intracellular calcium
IP3R
SOCE
RyR
STIM
ORAI

Published Papers (4 papers)

Download All Papers

Research

Jump to: Review

13 pages, 17235 KiB

Open AccessArticle

Altered Calcium Influx Pathways in Cancer-Associated Fibroblasts

by Francisco Sadras, Teneale A. Stewart, Mélanie Robitaille, Amelia A. Peters, Priyakshi Kalita-de Croft, Patsy S. Soon, Jodi M. Saunus, Sunil R. Lakhani, Sarah J. Roberts-Thomson and Gregory R. Monteith

Biomedicines 2021, 9(6), 680; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9060680 - 16 Jun 2021

Cited by 5 | Viewed by 2720

Abstract

Cancer-associated fibroblasts (CAFs) represent an important component of the tumour microenvironment and are implicated in disease progression. Two outstanding questions in cancer biology are how CAFs arise and how they might be targeted therapeutically. The calcium signal also has an important role in tumorigenesis. To date, the role of calcium signalling pathways in the induction of the CAF phenotype remains unexplored. A CAF model was generated through exogenous transforming growth factor beta 1 (TGFβ1) stimulation of the normal human mammary fibroblast cell line, HMF3S (HMF3S-CAF), and changes in calcium signalling were investigated. Functional changes in HMF3S-CAF calcium signalling pathways were assessed using a fluorescent indicator, gene expression, gene-silencing and pharmacological approaches. HMF3S-CAF cells demonstrated functionally altered calcium influx pathways with reduced store-operated calcium entry. In support of a calcium signalling switch, two voltage-gated calcium channel (VGCC) family members, Ca_V1.2 and Ca_V3.2, were upregulated in HMF3S-CAFs and a subset of patient-derived breast CAFs. Both siRNA-mediated silencing and pharmacological inhibition of Ca_V1.2 or Ca_V3.2 significantly impaired CAF activation in HMF3S cells. Our findings show that VGCCs contribute to TGFβ1-mediated induction of HMF3S-CAF cells and both transcriptional interference and pharmacological antagonism of Ca_V1.2 and Ca_V3.2 inhibit CAF induction. This suggests a potential therapeutic role for targeting calcium signalling in breast CAFs. Full article

(This article belongs to the Special Issue Calcium Signaling and Its Dysregulation in Cancer)

► Show Figures

Figure 1

16 pages, 16015 KiB

Open AccessArticle

A Novel Biomarker Driving Poor-Prognosis Liver Cancer: Overexpression of the Mitochondrial Calcium Gatekeepers

by Chia-Jung Li, Hung-Yu Lin, Chih-Jan Ko, Ji-Ching Lai and Pei-Yi Chu

Biomedicines 2020, 8(11), 451; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8110451 - 24 Oct 2020

Cited by 20 | Viewed by 2631

Abstract

Several studies have indicated the biological role of mitochondrial Ca²⁺ uptake in cancer pathophysiology; however, its implications in predicting the prognosis of hepatocellular carcinoma (HCC) are not yet fully understood. Here, we collected tumor specimens and adjacent normal liver tissues from 354 confirmed HCC patients and analyzed the levels of cyclic adenosine monophosphate (cAMP) responsive element binding protein 1 (CREB), mitochondrial calcium uniporter (MCU), mitochondrial calcium uptake 1 and 2 (MICU1, MICU2) using bioinformatics, qRT-PCR, and immunohistochemistry (IHC), and their relationship with clinicopathological characteristics and prognosis. HCC patients with low CREB/MICU1 and high MCU/MICU2 expression exhibited poor survival rate and prognosis in overall survival (OS) and disease-free survival (DFS) analyses. Low CREB/MICU1 and low MICU1 alone indicated poor prognosis in stage I/II and III/IV patients, respectively. In the poor differentiation/undifferentiation group, low expression of MICU1 indicated poor clinical outcomes. Low CREB/MICU1 expression suggested poor outcomes in patients with or without hepatitis B virus (HBV) infection and poor prognosis in the HCV infection group. In the non- hepatitis C virus (HCV) infection group, low MCU1 indicated a poor prognosis. Multivariate analysis demonstrated that CREB and MICU1 expression showed prognostic significance. This study demonstrates the prognostic significance of CREB, MCU, MICU1, and MICU2, in predicting HCC outcomes. Low CREB/MICU1 and high MCU/MICU2 in HCC tissues are associated with poor prognosis, thus offering a novel perspective in the clinical management for HCC patients. Full article

(This article belongs to the Special Issue Calcium Signaling and Its Dysregulation in Cancer)

► Show Figures

Figure 1

Review

Jump to: Research

59 pages, 7010 KiB

Open AccessReview

Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy

by Aarushi Sharma, Grace T. Ramena and Randolph C. Elble

Biomedicines 2021, 9(9), 1077; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091077 - 24 Aug 2021

Cited by 11 | Viewed by 4407

Abstract

Intracellular Ca²⁺ distribution is a tightly regulated process. Numerous Ca²⁺ chelating, storage, and transport mechanisms are required to maintain normal cellular physiology. Ca²⁺-binding proteins, mainly calmodulin and calbindins, sequester free intracellular Ca²⁺ ions and apportion or transport them to signaling hubs needing the cations. Ca²⁺ channels, ATP-driven pumps, and exchangers assist the binding proteins in transferring the ions to and from appropriate cellular compartments. Some, such as the endoplasmic reticulum, mitochondria, and lysosomes, act as Ca²⁺ repositories. Cellular Ca²⁺ homeostasis is inefficient without the active contribution of these organelles. Moreover, certain key cellular processes also rely on inter-organellar Ca²⁺ signaling. This review attempts to encapsulate the structure, function, and regulation of major intracellular Ca²⁺ buffers, sensors, channels, and signaling molecules before highlighting how cancer cells manipulate them to survive and thrive. The spotlight is then shifted to the slow pace of translating such research findings into anticancer therapeutics. We use the PubMed database to highlight current clinical studies that target intracellular Ca²⁺ signaling. Drug repurposing and improving the delivery of small molecule therapeutics are further discussed as promising strategies for speeding therapeutic development in this area. Full article

(This article belongs to the Special Issue Calcium Signaling and Its Dysregulation in Cancer)

► Show Figures

Graphical abstract

22 pages, 1414 KiB

Open AccessReview

From Orai to E-Cadherin: Subversion of Calcium Trafficking in Cancer to Drive Proliferation, Anoikis-Resistance, and Metastasis

by Aarushi Sharma and Randolph C. Elble

Biomedicines 2020, 8(6), 169; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8060169 - 21 Jun 2020

Cited by 11 | Viewed by 4363

Abstract

The common currency of epithelial differentiation and homeostasis is calcium, stored primarily in the endoplasmic reticulum, rationed according to need, and replenished from the extracellular milieu via store-operated calcium entry (SOCE). This currency is disbursed by the IP3 receptor in response to diverse extracellular signals. The rate of release is governed by regulators of proliferation, autophagy, survival, and programmed cell death, the strength of the signal leading to different outcomes. Intracellular calcium acts chiefly through intermediates such as calmodulin that regulates growth factor receptors such as epidermal growth factor receptor (EGFR), actin polymerization, and adherens junction assembly and maintenance. Here we review this machinery and its role in differentiation, then consider how cancer cells subvert it to license proliferation, resist anoikis, and enable metastasis, either by modulating the level of intracellular calcium or its downstream targets or effectors such as EGFR, E-cadherin, IQGAP1, TMEM16A, CLCA2, and TRPA1. Implications are considered for the roles of E-cadherin and growth factor receptors in circulating tumor cells and metastasis. The discovery of novel, cell type-specific modulators and effectors of calcium signaling offers new possibilities for cancer chemotherapy. Full article

(This article belongs to the Special Issue Calcium Signaling and Its Dysregulation in Cancer)

► Show Figures