Annexin A2 (ANXA2) (ANXA2)

Annexin A2 (ANXA2) is a calcium-dependent phospholipid-binding protein that acts as a versatile scaffold for various intracellular and extracellular signaling pathways, including the interaction with the transcription factor STAT3 (UniProt: P07355). In many aggressive cancers, such as triple-negative breast cancer and glioblastoma, ANXA2 is overexpressed and facilitates the phosphorylation and nuclear translocation of STAT3, thereby driving the expression of genes involved in cell survival, proliferation, and metastasis (PubMed: 26430173). The Annexin A2–STAT3 interface has emerged as a high-priority therapeutic target because disrupting this specific protein-protein interaction (PPI) can selectively inhibit oncogenic STAT3 signaling (PubMed: 31110044). Small molecule inhibitors, such as AOM-0901, are designed to bind to the ANXA2 surface and block the recruitment of STAT3, effectively suppressing tumor growth in preclinical models (PubMed: 31110044). Beyond its role in signal transduction, ANXA2 is involved in fibrinolysis and membrane trafficking, which presents potential safety challenges regarding systemic inhibition (UniProt: P07355). Targeting this interface represents a precision medicine strategy to modulate a traditionally difficult-to-target transcription factor by interfering with its essential co-factors.

Other names

Annexin IILipocortin IICalpactin I heavy chainChromobindin 8p36Protein IPlacental anticoagulant protein IV

Inhibition of the protein-protein interaction (PPI) between Annexin A2 and STAT3 to prevent STAT3 phosphorylation and nuclear translocation.