Activation of NOTCH signaling via DLL1 is mediated by APE1-redox-dependent NF-κB activation in oesophageal adenocarcinoma.

ABSTRACT:

Objective

Oesophageal adenocarcinoma (EAC) arises in the setting of Barrett's oesophagus, an intestinal metaplastic precursor lesion that can develop in patients with chronic GERD. Here, we investigated the role of acidic bile salts, the mimicry of reflux, in activation of NOTCH signaling in EAC.

Design

This study used public databases, EAC cell line models, L2-IL1β transgenic mouse model and human EAC tissue samples to identify mechanisms of NOTCH activation under reflux conditions.

Results

Analysis of public databases demonstrated significant upregulation of NOTCH signaling components in EAC. In vitro studies demonstrated nuclear accumulation of active NOTCH1 cleaved fragment (NOTCH intracellular domain) and upregulation of NOTCH targets in EAC cells in response to

SUBMITTER: Chen L 

PROVIDER: S-EPMC9789198 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature