Metabolic Profiling of Distinct -Mutant Esophageal Adenocarcinoma Models Reveals Different Bioenergetic Dependencies.

Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy with rising incidence and poor prognosis. , previously identified as the most frequently mutated gene in EAC in our studies, plays a central role in tumor suppression and regulation. However, the metabolic consequences of mutations in EAC remain largely uncharacterized. We metabolically profiled three -mutant EAC cell models (OE33, OE19, and FLO1) representing progressive stages of tumor differentiation and harboring distinct alterations. Our analyses revealed different metabolic phenotypes associated with status. OE33 cells predominantly use glycolytic metabolism but display limited adaptability to environmental changes, possibly due to a higher differentiation state. FLO1 cells exhibit a strong glycolytic dependence, elevated lactate production, and robust proliferation under acidic conditions, consistent with an aggressive and metastatic phenotype. OE19 cells preferentially utilize oxidative phosphorylation, demonstrated by resilience to glucose and glutamine deprivation, and ROS accumulation. These findings highlight the metabolic plasticity of EAC and suggest that mutation type might influence bioenergetic dependencies. Targeting these metabolic vulnerabilities may offer novel therapeutic avenues for personalized treatment in EAC.