VSIG2 hinders gastric cancer progression by suppressing ANXA2-mediated NF-κB pathway activation

• VSIG2 is significantly downregulated in gastric cancer tissues and correlates with poor prognosis, tumor size, lymph node metastasis, TNM stage, and vascular invasion. • VSIG2 suppresses gastric cancer cell proliferation, migration, and metastasis in vitro and in vivo. • Mechanistically, VSIG2 competes with FBXW10 for binding to ANXA2, promoting K63-linked polyubiquitination of ANXA2 and its membrane localization, thereby inactivating the NF-κB pathway. • This study identifies the VSIG2/ANXA2/NF-κB axis as a novel therapeutic target and potential biomarker for gastric cancer.