GRP78 and next generation cancer hallmarks: An underexplored molecular target in cancer chemoprevention research

Abstract

Glucose regulated protein 78 (GRP 78), a master regulator of endoplasmic reticulum stress has been reported to be up regulated in various cancers and remains a crucial link between tumor glycolysis and tumor microenvironment. Overexpressed GRP78 has also shown to induce immune suppressive molecules and thereby tumor immune evasion. On the other hand emerging reports indicates that the next generation hallmarks viz., metabolic reprogramming and immune evasion, the two distinct processes are suggested to be fundamentally linked which is yet to be explored. Our concern is, if GRP78 is considered as a connecting link between these two different processes then targeting this triangle would be a promising approach in anticancer drug discovery. Lack of sufficient literature on this aspect represents GRP78 as an under explored target in anti-cancer research. The objective of this review is to provide a concise and integrated information on GRP78 and its association with tumor glycolysis and immune evasion which will revive and draw attention of the researchers to consider GRP78 as a potential drug target for cancer intervention and it also highlights few potential natural products investigated so far as GRP78 inhibitors.

Keywords: Carcinogenesis; GRP78 inhibitors; Glucose regulated protein 78; Metabolic reprogramming; Next generation hallmarks; Tumor immune evasion.