Lactate Suppresses Growth of Esophageal Adenocarcinoma Patient-Derived Organoids through Alterations in Tumor NADH/NAD+ Redox State.

ABSTRACT: Barrett's esophagus (BE) is a common precancerous lesion that can progress to esophageal adenocarcinoma (EAC). There are significant alterations in the esophageal microbiome in the progression from healthy esophagus to BE to EAC, including an increased abundance of a variety of lactate-producing bacteria and an increase of lactate in the tumor microenvironment, as predicted by metabolic modeling. The role of bacterial lactate in EAC is unknown. Here, we utilize patient-derived organoid (PDO) models of EAC and demonstrate that lactate inhibits the growth and proliferation of EAC PDOs through alterations in the tumor NADH/NAD+ redox state. Further RNA sequencing of EAC PDOs identifies ID1 and RSAD2 as potential regulatory molecules crucial in mediating lactate's ability to suppress glycolysi

SUBMITTER: Su SH 

PROVIDER: S-EPMC11430592 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature