Next Article in Journal
Impact of Local High Doses of Radiation by Neutron Activated Mn Dioxide Powder in Rat Lungs: Protracted Pathologic Damage Initiated by Internal Exposure
Previous Article in Journal
The Effect of Sleeve Gastrectomy on Oxidative Stress in Obesity
Open AccessReview

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

1
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
2
Department of Pharmacology and Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
*
Author to whom correspondence should be addressed.
Biomedicines 2020, 8(6), 169; https://doi.org/10.3390/biomedicines8060169
Received: 27 May 2020 / Revised: 17 June 2020 / Accepted: 19 June 2020 / Published: 21 June 2020
(This article belongs to the Special Issue Calcium Signaling and Its Dysregulation in Cancer)
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. View Full-Text
Keywords: calcium; SOCE; SICE; IP3R; Orai; Stim; EGFR; E-cadherin; IQGAP; calmodulin; anoikis; circulating tumor cells calcium; SOCE; SICE; IP3R; Orai; Stim; EGFR; E-cadherin; IQGAP; calmodulin; anoikis; circulating tumor cells
Show Figures

Graphical abstract

MDPI and ACS Style

Sharma, A.; Elble, R.C. From Orai to E-Cadherin: Subversion of Calcium Trafficking in Cancer to Drive Proliferation, Anoikis-Resistance, and Metastasis. Biomedicines 2020, 8, 169.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop