Role of G2A in Intestinal Inflammation and Colon Cancer Grant uri icon

abstract

  • Tumor development is a complex process influenced by genes and environmental factors. Chronic inflammation, as illustrated in inflammatory bowel disease (IBD), is an important risk factor that can predispose susceptible chronically inflamed cells to oncogenic transformation, leading to tumor formation. As such, anti-inflammatory agents have been evaluated for cancer prevention. The proton-sensing G protein-coupled receptors, including GPR4, TDAG8 (GPR65), OGR1 (GPR68), and G2A (GPR132), have emerged as important regulators of inflammation and tumorigenesis. Agonists and antagonists of these receptors are being actively developed and evaluated for potential therapeutic applications. G2A is highly expressed in immune cells and plays critical roles in inflammatory response, autoimmunity, and cancer. G2A has also been implicated as a receptor involved in acute intestinal inflammation and gut microbiome-host interactions. However, little is known on the role of this receptor in chronic intestinal inflammation and inflammation associated colorectal cancer (CRC). Our preliminary results showed that G2A deficiency exacerbated intestinal inflammation in a chronic IBD mouse model, suggesting G2A is a crucial regulator of IBD. In this proposal we aim to delineate the function and mechanism by which G2A modulates intestinal inflammation and CRC development. Additionally, we will characterize the therapeutic effects of G2A agonists in the modulation of G2A activity in chronic intestinal inflammation and CRC development.

date/time interval

  • January 2017 - December 2017