Annexin A1 (ANXA1) (ANXA1)

Annexin A1 (ANXA1) is a 37 kDa calcium-dependent phospholipid-binding protein that serves as a primary effector of the anti-inflammatory actions of glucocorticoids. It is normally localized in the cytoplasm but is secreted upon cellular activation or glucocorticoid stimulation to act in an autocrine or paracrine manner. ANXA1 primarily signals through the formyl peptide receptor 2 (FPR2/ALX) to inhibit leukocyte adhesion and migration, promote neutrophil apoptosis, and enhance the clearance of apoptotic cells, thereby facilitating the resolution of inflammation. Beyond its role in the immune system, ANXA1 is involved in various cellular processes including membrane trafficking, cell proliferation, and apoptosis. In the context of disease, ANXA1 exhibits a complex, tissue-specific role. In many cancers, such as triple-negative breast cancer and pancreatic cancer, ANXA1 is overexpressed and acts as an oncogene by promoting tumor growth, angiogenesis, and immune evasion. This has led to the development of targeted therapies like the monoclonal antibody MDX-124, which aims to neutralize its pro-tumorigenic effects. Conversely, in inflammatory and cardiovascular diseases, ANXA1 and its mimetic peptides (e.g., Ac2-26) are being explored for their therapeutic potential to resolve chronic inflammation and protect against ischemia-reperfusion injury. The protein also serves as a valuable biomarker, notably for the diagnosis of hairy cell leukemia and as a prognostic indicator in conditions like COVID-19 and heart failure.

Other names

Lipocortin ICalpactin IIChromobindin-9Annexin IAnnexin-1Phospholipase A2 inhibitory proteinp35LPC1ANX1

Glucocorticoids induce the expression and secretion of Annexin A1, which then binds to Formyl peptide receptor 2 (FPR2/ALX) to mediate anti-inflammatory and pro-resolving effects. It also inhibits cytosolic Phospholipase A2 (cPLA2), thereby reducing the production of pro-inflammatory eicosanoids like prostaglandins and leukotrienes. In oncology, therapeutic antibodies like MDX-124 bind to and neutralize extracellular Annexin A1 to block its oncogenic signaling through formyl peptide receptors, which otherwise promotes tumor growth and immune evasion.