Annexin A1 localization and its relevance to cancer

Annexin A1 (ANXA1) is a Ca2+-regulated phospholipid-binding protein involved in various cell processes. ANXA1 was initially widely studied in inflammation resolution, but its overexpression was later reported in a large number of cancers. Further in-depth investigations have revealed that this protein could have many roles in cancer progression and act at different levels (from cancer initiation to metastasis). This is partly due to the location of ANXA1 in different cell compartments. ANXA1 can be nuclear, cytoplasmic and/or membrane associated. This last location allows ANXA1 to be proteolytically cleaved and/or to become accessible to its cognate partners, the formyl-peptide receptors. Indeed, in some cancers, ANXA1 is found at the cell surface, where it stimulates formyl-peptide receptors to trigger oncogenic pathways. In the present review, we look at the different locations of ANXA1 and their association with the deregulated pathways often observed in cancers. We have specifically detailed the non-classic pathways of ANXA1 externalization, the significance of its cleavage and the role of the ANXA1–formyl-peptide receptor complex in cancer progression. * AA, : arachidonic acid; ABC, : ATP-binding cassette; Akt, : protein kinase B; ANXA1, : annexin A1; BLBC, : basal-like breast cancer cell; DFS, : disease-free survival; EGFR, : epidermal growth factor receptor; EMT, : epithelial–mesenchymal transition; ER, : endoplasmic reticulum; ERK, : extracellular signal-related kinase; FPR, : formyl-peptide receptor; GC, : gastric cancer; HIF, : hypoxia-inducible transcription factor; Iβ1BP1, : integrin β1-binding protein 1; MAPK, : mitogen-activated protein kinase; MMS, : methyl methanesulfonate; MP, : microparticle; MVE, : multivesicular endosome; NES, : nuclear export signal; PAF-AH, : platelet activating factor–acyl hydrolase; PKC, : protein kinase C; PLA2, : phospholipase A2; PM, : plasma membrane; PMA, : phorbol 12-myristate 13-acetate; PMN, : polymorphonucleocyte; TLS, : translesion synthesis; VEGF, : vascular endothelial growth factor; ZA, : zoledronic acid