Signal Transduction in Barrett’s Esophagus and Esophageal Adenocarcinoma

Abstract

Barrett’s esophagus (BE) is a pre-malignant state that can proceed to the cancerous condition known as esophageal adenocarcinoma (EA). The molecular pathogenesis from the normal esophagus to BE and its progression from BE to EA is poorly understood making the diagnoses and treatment suboptimal. It is known that chronic gastro-esophageal reflux of bile acids is a trigger of BE and what initiates the epithelial metaplastic change. There has been increasing evidence in regards to the abnormal signaling seen during the development of BE that resembles to signaling pathways present during the embryological development of the esophagus. The signaling pathways seen during development of the esophagus are as follows: Bone morphogenetic protein signaling (BMP), Hedgehog signaling (HH), Wingless-Type MMTV Integration Site Family (WNT), Retinoic acid signaling pathway (RA) and Notch signaling. Importantly, in vivo and in vitro models have demonstrated that, in the presence of bile acids, these abnormal signaling pathways are induced. Although the signaling pathways mentioned are involved during the development of the esophagus from simple columnar to stratified squamous epithelium, then these same signaling pathways but in reverse should help better understand the molecular pathogenesis involved in the development of BE from stratified squamous to simple columnar.