Boudhraa Zied, Bouchon Bernadette, Viallard Claire, D'Incan Michel, Degoul Françoise
Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France INSERM, U 990, F-63000 Clermont-Ferrand, France
Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France INSERM, U 990, F-63000 Clermont-Ferrand, France.
Clin Sci (Lond). 2016 Feb;130(4):205-20. doi: 10.1042/CS20150415.
Annexin A1 (ANXA1) is a Ca(2+)-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.
膜联蛋白A1（ANXA1）是一种受Ca（2+）调节的磷脂结合蛋白，参与多种细胞过程。ANXA1最初在炎症消退方面得到广泛研究，但后来有报道称其在大量癌症中过度表达。进一步深入研究发现，这种蛋白在癌症进展中可能具有多种作用，并在不同水平发挥作用（从癌症发生到转移）。这部分归因于ANXA1在不同细胞区室中的定位。ANXA1可以与细胞核、细胞质和/或细胞膜相关联。最后这种定位使得ANXA1能够被蛋白水解切割和/或与其同源伴侣甲酰肽受体结合。实际上，在某些癌症中，ANXA1存在于细胞表面，在那里它刺激甲酰肽受体触发致癌途径。在本综述中，我们探讨了ANXA1的不同定位及其与癌症中经常观察到的失调途径的关联。我们特别详细阐述了ANXA1外化的非经典途径、其切割的意义以及ANXA1-甲酰肽受体复合物在癌症进展中的作用。
