Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
3.7
4.7
Journals
Biomedicines
Special Issues
Calcium Signaling and Its Dysregulation in Cancer 2.0
share announcement

Calcium Signaling and Its Dysregulation in Cancer 2.0

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

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 4857

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,

The role that intracellular calcium plays in both tumor suppression and progression has earned more appreciation. 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 many growth-promoting effects.

This Special Issue invites both original manuscripts which describe novel findings and cutting-edge review articles which illustrate 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.

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 (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

13 pages, 4923 KiB  
Article
Self-Cleavage of Human Chloride Channel Accessory 2 Causes a Conformational Shift That Depends on Membrane Anchorage and Is Required for Its Regulation of Store-Operated Calcium Entry
by Grace T. Ramena, Aarushi Sharma, Yan Chang, Zui Pan and Randolph C. Elble
Biomedicines 2023, 11(11), 2915; https://doi.org/10.3390/biomedicines11112915 - 28 Oct 2023
Viewed by 915
Abstract
Human CLCA2 regulates store-operated calcium entry (SOCE) by interacting with Orai1 and STIM1. It is expressed as a 943aa type I transmembrane protein that is cleaved at amino acid 708 to produce a diffusible 100 kDa product. The N-terminal ectodomain contains a hydrolase-like [...] Read more.
Human CLCA2 regulates store-operated calcium entry (SOCE) by interacting with Orai1 and STIM1. It is expressed as a 943aa type I transmembrane protein that is cleaved at amino acid 708 to produce a diffusible 100 kDa product. The N-terminal ectodomain contains a hydrolase-like subdomain with a conserved HEXXH zinc-binding motif that is proposed to cleave the precursor autoproteolytically. Here, we tested this hypothesis and its link to SOCE. We first studied the conditions for autocleavage in isolated membranes and then in a purified protein system. Cleavage was zinc-dependent and abolished by mutation of the E in the HEXXH motif to Q, E165Q. Cleavage efficiency increased with CLCA2 concentration, implying that it occurs in trans. Accordingly, the E165Q mutant was cleaved by co-transfected wildtype CLCA2. Moreover, CLCA2 precursors with different epitope tags co-immunoprecipitated. In a membrane-free system utilizing immunopurified protease and target, no cleavage occurred unless the target was first denatured, implying that membranes provide essential structural or conformational cues. Unexpectedly, cleavage caused a conformational shift: an N-terminal antibody that immunoprecipitated the precursor failed to precipitate the N-terminal product unless the product was first denatured with an ionic detergent. The E165Q mutation abolished the stimulation of SOCE caused by wildtype CLCA2, establishing that the metalloprotease activity is required for this regulatory function. Full article
(This article belongs to the Special Issue Calcium Signaling and Its Dysregulation in Cancer 2.0)
►▼ Show Figures

Figure 1

15 pages, 2306 KiB  
Article
Targeting Store-Operated Calcium Entry Regulates the Inflammation-Induced Proliferation and Migration of Breast Cancer Cells
by Mohammed Alqinyah, Abdullah S. Alhamed, Hajar O. Alnefaie, Mohammad M. Algahtani, Amira M. Badr, Abdullah M. Albogami, Mohamed Mohany, Yasseen A. Alassmrry, Adel F. Alghaith, Hussain N. Alhamami, Khalid Alhazzani, Ahmed Z. Alanazi and Omar Awad Alsaidan
Biomedicines 2023, 11(6), 1637; https://doi.org/10.3390/biomedicines11061637 - 04 Jun 2023
Cited by 3 | Viewed by 1732
Abstract
Persistent challenges complicating the treatment of breast cancer remain, despite some recent undeniable successes. Sufficient evidence currently exists demonstrating the crucial role of inflammation, characterized by the enhanced activation of Toll-like receptor 4 (TLR4) and the COX-2/PGE2 pathway, in the migration and proliferation [...] Read more.
Persistent challenges complicating the treatment of breast cancer remain, despite some recent undeniable successes. Sufficient evidence currently exists demonstrating the crucial role of inflammation, characterized by the enhanced activation of Toll-like receptor 4 (TLR4) and the COX-2/PGE2 pathway, in the migration and proliferation of breast cancer cells. Interestingly, the store-operated calcium entry (SOCE) pathway was shown to be essential for the TLR4 activity and COX-2 expression in immune cells such as macrophages and microglia. However, whether SOCE influences inflammatory signaling and the inflammation-induced proliferation and migration of breast cancer cells is still unknown. Thus, the current study intended to delineate the role of SOCE in the TLR4-induced inflammation, migration, and proliferation of breast cancer cells. To this end, MDA-MB-231 breast cancer cells were treated with lipopolysaccharide (LPS) to activate TLR4, BTP2 to inhibit SOCE, and Thapsigargin to induce SOCE. Following these treatments, several experiments were conducted to evaluate the proliferation and migration rates of the MDA-MB-231 cells and the expression of several inflammatory and oncogenic genes, including COX-2, PGE2, IL-6, IL-8, and VEGF. Different techniques were used to achieve the aims of this study, including qRT-PCR, Western blotting, ELISA, MTT, and wound healing assays. This study shows that SOCE inhibition using BTP2 suppressed the LPS-induced migration and proliferation of breast cancer cells. Additionally, treatment with LPS caused approximately six- and three-fold increases in COX-2 mRNA and protein expression, respectively, compared to the controls. The LPS-induced elevations in the COX-2 mRNA and protein levels were suppressed by BTP2 to the control levels. In addition to its effect on COX-2, BTP2 also suppressed the LPS-induced productions of PGE2, IL-6, IL-8, and VEGF. Conversely, SOCE induction using Thapsigargin enhanced the LPS-induced inflammation, migration, and proliferation of breast cancer cells. Collectively, these results provide evidence for the potentially important role of SOCE in inflammation-induced breast cancer progression processes. Thus, we argue that the current study may provide novel targets for designing new therapeutic approaches for the treatment of breast cancer. Full article
(This article belongs to the Special Issue Calcium Signaling and Its Dysregulation in Cancer 2.0)
►▼ Show Figures

Figure 1

Review

Jump to: Research

17 pages, 2497 KiB  
Review
Regulation of ErbB Receptors by the Ca2+ Sensor Protein Calmodulin in Cancer
by Antonio Villalobo
Biomedicines 2023, 11(3), 661; https://doi.org/10.3390/biomedicines11030661 - 22 Feb 2023
Cited by 1 | Viewed by 1805
Abstract
Overexpression and mutations of the epidermal growth factor receptor (EGFR/ErbB1/HER1) and other tyrosine kinase receptors of the ErbB family (ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4) play an essential role in enhancing the proliferation, the migratory capacity and invasiveness of many tumor cells, leading to cancer [...] Read more.
Overexpression and mutations of the epidermal growth factor receptor (EGFR/ErbB1/HER1) and other tyrosine kinase receptors of the ErbB family (ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4) play an essential role in enhancing the proliferation, the migratory capacity and invasiveness of many tumor cells, leading to cancer progression and increased malignancy. To understand these cellular processes in detail is essential to understand at a molecular level the signaling pathways and regulatory mechanisms controlling these receptors. In this regard, calmodulin (CaM) is a Ca2+-sensor protein that directly interacts with and regulates ErbB receptors, as well as some CaM-dependent kinases that also regulate these receptors, particularly EGFR and ErbB2, adding an additional layer of CaM-dependent regulation to this system. In this short review, an update of recent advances in this area is presented, covering the direct action of Ca2+/CaM on the four ErbB family members mostly in tumor cells and the indirect action of Ca2+/CaM on the receptors via CaM-regulated kinases. It is expected that further understanding of the CaM-dependent mechanisms regulating the ErbB receptors in future studies could identify new therapeutic targets in these systems that could help to control or delay cancer progression. Full article
(This article belongs to the Special Issue Calcium Signaling and Its Dysregulation in Cancer 2.0)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop