Assessing the endoplasmic reticulum oxidoreductase-1 alpha in human cancer cells

Abstract

Background: In the endoplasmic reticulum (ER), protein folding is a highly important process, which maintains proper maturation of secretory and membrane proteins(Schwarz & Blower, 2015). Formation of disulfide bonds helps to stabilize the protein structure and this process is regulated by a network of the ER oxidoreductases (Oka & Bulleid, 2013). ERO1α (endoplasmic reticulum oxidoreductin-1 alpha) is one of them and it is one of the most important ER-resident flavoproteins that promote oxidative protein folding by re-oxidizing protein disulfide isomerase (PDI) and produces reactive oxygen species (ROS) as a byproduct (Appenzeller‐Herzog et al., 2010). The malfunction of this pathway has been gaining more and more links with cancer development whereby tumor cells manifest high secretory needs and disturbed redox homeostasis. Methods: This paper is a research conducted into the expressions of ERO1α in a number of human cancer cell lines and how it may be involved in redox regulation of tumors. The expression of ERO1α at the mRNA level was measured with the help of quantitative real-time PCR (RT-qPCR), whereas the level of protein was measured with the help of Western blot analysis. Also, Kaplan-Meier analysis was done to see the survival rate regarding ERO1α expression. A comparison between the various cancer cell models indicated that the expression pattern is variable, and it is possible that ERO1α can be used in tumor-specific adaptation in the oxidative folding of proteins and ER stress responses. Results: The results are in favour of the notion that ERO1α -PDI redox interface is important in the process of preserving ER proteostasis during high protein folding stress in cancer cells. Knowledge of the regulation of this pathway can offer an insight into tumor biology and be of significance in providing therapeutic targets with the aim to disrupt redox-dependent protein folding in malignancies.