Oxaloacetate stimulates phosphorylation of epidermal growth factor receptor in epithelial cells in vitro

Oxaloacetate (OA) is a pivotal endogenous metabolite. Within our investigation, we ascertained that OA functions as an agonist for the epidermal growth factor receptor (EGFR), a key protagonist in the genesis of diverse tumours. We substantiated that escalating concentrations of OA initially enhanced the cellular viability of several cancer cells, followed by subsequent attenuation, which is similar to the effect of EGF. Furthermore, the protein phosphorylation profile in HepG2 cells exposed to OA closely paralleled that induced by epidermal growth factor (EGF). Additional findings underscored the capability of OA to induce the generation of EGFR dimers. Finally, our observations revealed that OA governs the activation of AKT and Erk, the typical downstream signalling proteins of EGFR. We postulate that the endogenous metabolite OA can function as either an agonist or inhibitor of EGFR at specific concentrations to modulate tumour proliferation, and provide new insights into the regulation of EGFR activation.