2026-10-10T23:10:47Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33770016 2026-09-15T03:05:58Z category_1 category_4 category_7 category_12 category_13 category_14 category_16 category_19 category_873 category_64 category_132 category_134 category_135 portal_63 item_type_3 month_year_09_2026

Integrated Metabolomic, Proteomic, and Phosphoproteomic Profiling Reveals Metabolic and Signaling Alterations Associated with CAMKK2 Inhibition in Gastric Cancer Mohd Altaf Najar (10580547) Nikita Choudhary (23186755) Nidhi Dwivedi (4774908) Prashant Kumar Modi (7359551) Biophysics Biochemistry Medicine Cell Biology Genetics Molecular Biology Physiology Pharmacology Chemical Sciences not elsewhere classified Cancer Infectious Diseases Virology Computational Biology pyrimidine intermediates required potential therapeutic target pathway analysis demonstrated central carbon metabolism cell cycle progression signaling pathways involved aberrant kinase signaling integrated multiomics approach camkk2 using sto signaling programs associated promotes uncontrolled proliferation exploiting metabolic vulnerabilities findings highlight camkk2 signaling alterations associated impaired dna replication gastric cancer cells dna replication machinery associated signaling phosphoproteomic alterations integrated metabolomic gastric cancer findings suggest dna synthesis dna replication camkk2 inhibition camkk2 contributes untargeted metabolomics regulating tumor pharmacological inhibition metabolic adaptations like phenotype coordinated metabolic although calcium 609 resulted Gastric cancer is driven by aberrant kinase signaling that promotes uncontrolled proliferation and metabolic adaptations. 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. Integration with proteomic and phosphoproteomic datasets revealed coordinated downregulation of DNA replication machinery and attenuation of signaling pathways involved in cell cycle progression. Collectively, these findings suggest that CAMKK2 contributes to the coordination of metabolic and signaling programs associated with DNA replication and proliferation in gastric cancer. CAMKK2 inhibition was associated with the coordinated depletion of nucleotide metabolites and disruption of replication-associated signaling, consistent with impaired DNA replication and a replication-stress-like phenotype. These findings highlight CAMKK2 as a potential therapeutic target for exploiting metabolic vulnerabilities in gastric cancer. 2026-09-14T00:00:00Z Dataset Dataset 10.1021/acs.jproteome.6c00428.s003 https://figshare.com/articles/dataset/Integrated_Metabolomic_Proteomic_and_Phosphoproteomic_Profiling_Reveals_Metabolic_and_Signaling_Alterations_Associated_with_CAMKK2_Inhibition_in_Gastric_Cancer/33770016 CC BY-NC 4.0