# Metabolic Profiling of Distinct TP53-Mutant Esophageal Adenocarcinoma Models Reveals Different Bioenergetic Dependencies

## TL;DR

This study explores how different TP53 mutations in esophageal cancer cells affect their metabolism, revealing varied energy dependencies that could guide personalized treatments.

## Contribution

The study identifies distinct metabolic profiles linked to specific TP53 mutations in esophageal adenocarcinoma models.

## Key findings

- OE33 cells rely on glycolysis but show limited metabolic flexibility.
- FLO1 cells exhibit aggressive glycolytic metabolism and thrive in acidic environments.
- OE19 cells prefer oxidative phosphorylation and resist nutrient deprivation.

## Abstract

Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy with rising incidence and poor prognosis. TP53, 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 TP53 mutations in EAC remain largely uncharacterized. We metabolically profiled three TP53-mutant EAC cell models (OE33, OE19, and FLO1) representing progressive stages of tumor differentiation and harboring distinct TP53 alterations. Our analyses revealed different metabolic phenotypes associated with TP53 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 TP53 mutation type might influence bioenergetic dependencies. Targeting these metabolic vulnerabilities may offer novel therapeutic avenues for personalized treatment in EAC.