ANXA9 (Annexin A9) is a calcium-dependent phospholipid-binding protein that functions primarily as an oncogenic driver in multiple cancer types. In breast cancer, ANXA9 promotes tumor progression by facilitating S100A4 expression and modulating the AKT/mTOR/STAT3 pathway, while also mediating cytokine excretion (IL-6, IL-8, CCL2, CCL5) through phosphorylation at Ser2 and Thr69 to enhance angiogenesis 1. ANXA9 is secreted via exosomes, with exosome-derived ANXA9 increasing cellular uptake 1-7 fold in breast cancer cells, promoting proliferation, migration, and invasion 2. The miR-186-5p-ANXA9 axis represents a regulatory mechanism, where miR-186-5p suppresses ANXA9 to inhibit tumorigenesis and induce apoptosis 3. In colorectal cancer, ANXA9 promotes proliferation through the Wnt signaling pathway and enhances invasion/metastasis by upregulating ADAM17 and MMP-9 while downregulating tissue inhibitors and E-cadherin 45. In gastric cancer, ANXA9 drives proliferation and migration via TGF-β signaling and is associated with poor prognosis and immune infiltrates 67. Additionally, ANXA9 upregulation correlates with cisplatin resistance in ovarian cancer, with miR-105-1 targeting ANXA9 to restore chemosensitivity 8. These findings establish ANXA9 as a multifunctional oncogene with therapeutic potential across multiple cancer types.