Putting oesophageal cancer on the RACK A study of the RACK1 scaffolding protein in oesophageal adenocarcinoma

Abstract

Purpose There is a need to identify new therapeutic targets for oesophageal adenocarcinoma. Deoxycholic acid is a component of gastro-oesophageal refluxate and is believed to promote oesophageal adenocarcinoma. RACK1 is an intracellular scaffolding protein whose expression is altered in many cancers. The role of RACK1 in oesophageal adenocarcinoma has not been investigated. The purpose of this study is to examine the expression of RACK1 in oesophageal adenocarcinoma and to assess its potential as a contributor to this disease. This study also aims to investigate if deoxycholic acid modulates RACK1 in oesophageal adenocarcinoma cells. Methods Normal oesophageal epithelial cell lines, Barrett’s metaplastic and dysplastic cell lines and oesophageal adenocarcinoma cell lines were used to construct a model of oesophageal adenocarcinoma disease progression. RACK1 expression levels were assessed by western blotting. RACK1 subcellular localisation was examined by immunofluorescent confocal microscopy. Results RACK1 protein levels generally increase with increasing disease progression across a panel of cell lines representing the multistep sequence from normal oesophagus to oesophageal adenocarcinoma. Deoxycholic acid downregulates RACK1 protein levels in SKGT-4 (31% reduction; P=0.01) and FLO-1 (26% reduction; P=0.03) oesophageal adenocarcinoma cells. RACK1 has a diffuse, cytoplasmic localisation in SKGT-4 and FLO-1 cells and is most concentrated in the perinuclear area. This pattern of RACK1 subcellular localisation is not altered by deoxycholic acid Conclusion RACK1 may be upregulated during the development of oesophageal adenocarcinoma. Deoxycholic acid can modulate RACK1 protein levels in oesophageal adenocarcinoma cells. RACK1 may contribute to the progression of oesophageal adenocarcinoma and further investigation into its role in this disease is warranted.