AURKA-Driven Metabolic Rewiring in Gastric Epithelial Cells

Abstract

Gastric cancer (GC) accounts for a substantial portion of cancer-related mortality worldwide. Aurora kinase A (AURKA) plays a crucial role in mitotic progression and is overexpressed in various cancers, including GC. This study aimed to characterise the metabolic alterations associated with AURKA modulation in gastric epithelial cells. To understand this, we employed a multi-omics approach, integrating Raman microspectroscopy and LC–MS-based metabolomics and lipidomics, and further analyses have been performed using MetaboAnalyst 6.0. Our findings reveal that AURKA overexpression, its mutants and AURKA knockdown induce a significant metabolic alteration. LC–MS showed a significant change in 15 metabolites and 24 lipid molecules in cells transfected with AURKA-wt and mutants, whereas 36 metabolites and 22 lipids were altered in shA-transfected AGS cells. Moreover, various biomolecular peaks were found to be significantly altered in nuclear as well as peripheral regions of these cells when subjected to Raman microspectroscopy. These alterations led to the change in key metabolic pathways such as glycerophospholipid metabolism, sphingolipid metabolism and amino acid metabolism. These metabolic shifts indicate AURKA's role in promoting cancer cell proliferation and survival. Further, Raman peak shift also signifies the change in specific metabolites between AURKA-wt, its mutants and knockdown sample. Additionally, we identified alanine, glycine, urea, L-proline and citric acid as the potential biomarkers in AURKA-induced GC cells. Together, these findings underscore the importance of AURKA in metabolic regulation during gastric carcinogenesis and highlight the utility of metabolic profiling in identifying novel therapeutic targets for GC. © 2026 John Wiley & Sons, Ltd.