Gastric cancer (GC) is the third highest cause of cancer-related death worldwide and is often only diagnosed when the genetic alterations are already irreversible.
NFkB1 is a transcription factor implicated in regulating cellular proliferation, inflammation and senescence. NFkB1 polymorphisms have been associated with the inflammation process preceding GC establishment and phenotypes observed in a NFkB1-/-mouse model clearly demonstrate the role of NFkB1 in modulating inflammation.
The gastric epithelium has a high turnover which is fuelled and controlled by gastric stem cell (GSC) populations found in the isthmus and in the base of gastric glands.
In order to analyse the effect of NFkB1 loss in GSCs, gastric organoids are employed in this project. Analysis of the effects of NFkB1 loss in the mouse model suggest interactions between the immune system and the epithelium are crucial for tumorigenic evolution. Organoid cultures provide an opportunity to investigate epithelial cell-specific phenotypes and analyse specific effects on GSCs through flow cytometry, immunofluorescence and functional assays. Gaining insight into the mechanisms of NFkB1 action may lead to the development of intervention options to interrupt the progression of inflammation to gastric cancer.