LITAF-NOTCH2-Bmi-1 Axis Mediates AMPK-Dependent Inhibition of Gastric Cancer Invasion and Metastasis.

While AMPK activation is linked to suppressed tumor metastasis, its mechanistic interplay with gastric cancer (GC) progression remains unclear. This study elucidates how the LITAF-NOTCH2-Bmi-1 axis mediates AMPK-dependent inhibition of GC invasion and metastasis. Immunohistochemistry assessed p-AMPK, LITAF, and Bmi-1 expression in GC/adjacent tissues. TCGA data evaluated clinical correlations. LKB1 overexpression/knockout and AMPK modulators (berberine/AIC/Compound C) were used to dissect AMPK/LITAF/Bmi-1 signaling. Functional assays (proliferation, migration, and invasion) and xenograft models validated LITAF's role. Double gene rescue (LITAF/NOTCH2) clarified Bmi-1 regulation. GC tissues exhibited decreased LITAF/p-AMPK and elevated Bmi-1/NOTCH2, correlating with advanced pathology. LKB1/AMPK activation upregulated LITAF, suppressing Bmi-1. LITAF overexpression inhibited GC proliferation, migration, and invasion in vitro and delayed tumor growth in vivo. Patients with low LITAF/high Bmi-1 had the poorest survival, with both markers as independent prognostic factors (Cox regression). Mechanistically, LITAF required NOTCH2 to suppress Bmi-1, and AMPK's antitumor effects were LITAF-dependent. The LITAF-NOTCH2-Bmi-1 axis is critical for AMPK-mediated suppression of GC metastasis. Targeting this cascade offers therapeutic potential for GC management.