Integrated Metabolomic, Proteomic, and Phosphoproteomic Profiling Reveals Metabolic and Signaling Alterations Associated with CAMKK2 Inhibition in Gastric Cancer

Although calcium/calmodulin-dependent protein kinase 2 (CAMKK2) is overexpressed in gastric cancer, its role in regulating tumor-associated metabolic programs remains unclear. Here, we employed an integrated multiomics approach, centered on untargeted metabolomics, to investigate the effects of CAMKK2 inhibition in gastric cancer cells.

Pharmacological inhibition of CAMKK2 using STO-609 resulted in G1/S phase cell cycle arrest, multinucleation, and coordinated metabolic, proteomic, and phosphoproteomic alterations. Metabolomic profiling revealed extensive metabolic reprogramming characterized by the depletion of purine and pyrimidine intermediates required for DNA synthesis. Pathway analysis demonstrated the suppression of nucleotide, lipid, and central carbon metabolism, indicating impaired biosynthetic capacity.