Minireviews
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. Jul 27, 2015; 5(2): 78-85
Published online Jul 27, 2015. doi: 10.5411/wji.v5.i2.78
GRP78 expression beyond cellular stress: A biomarker for tumor manipulation
Britta Hardy, Annat Raiter
Britta Hardy, Annat Raiter, Felsenstein Medical Research Center, Tel-Aviv University School of Medicine, Rabin Medical Center, Petach Tikva 49100, Israel
Author contributions: Hardy B and Raiter A designed, performed, analyzed and wrote the paper.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Britta Hardy, PhD, Professor, Director, Felsenstein Medical Research Center, Tel-Aviv University School of Medicine, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel. brittah23@gmail.com
Telephone: +972-54-7527482 Fax: +972-3-6419735
Received: December 7, 2014
Peer-review started: December 9, 2014
First decision: December 26, 2014
Revised: January 14, 2015
Accepted: June 4, 2015
Article in press: June 8, 2015
Published online: July 27, 2015
Processing time: 239 Days and 17.4 Hours
Abstract

Physiological stress takes place in the endoplasmic reticulum (ER) of cells where activation and up-regulation of genes and proteins are primarily induced to enhance pro-survival mechanisms such as the unfolded protein response (UPR). A dominant protein in the UPR response is the heat shock GRP78 protein. Although GRP78 is primarily located in the ER, under certain conditions it is transported to the cell surface, where it acts as a receptor inducing pathways of cell signaling such as proliferation or apoptosis. In the prolonged chronic stress transportation of the GRP78 from the ER to the cell membrane is a major event where in addition to the presentation of the GRP78 as a receptor to various ligands, it also marks the cells that will proceed to apoptotic pathways. In the normal cell that under stress acquires cell surface GRP78 and in the tumor cell that already presents cell surface GRP78, cell surface GRP78 is an apoptotic flag. The internalization of GRP78 from the cell surface in normal cells by ligands such as peptides will enhance cell survival and alleviate cardiovascular ischemic diseases. The absence of cell surface GRP78 in the tumor cells portends proliferative and metastatic tumors. Pharmacological induction of cell surface GRP78 will induce the process of apoptosis and might be used as a therapeutic modality for cancer treatment.

Keywords: Cell surface GRP78; Apoptosis; Endoplasmic reticulum stress; Tumor cells; Cancer; Cardiovascular ischemia; Hypoxia

Core tip: In the prolonged chronic stress transportation of the GRP78 from the endoplasmic reticulum to the cell membrane is a major event where in addition to the presentation of the GRP78 as a receptor to various ligands, it also marks the cells that will proceed to apoptotic pathways. In the normal cell that under stress acquires cell surface GRP78 and in the tumor cell that already presents cell surface GRP78, cell surface GRP78 is an apoptotic flag. This review analyzes the input of cell surface GRP78 on apoptosis in normal and tumor cells.