Annexin A1, A2, A5, and A6 involvement in human pathologies

Abstract

The human genome codes for 12 annexins with highly homologous membrane‐binding cores and unique amino termini, which endow each protein with its specific biological properties. Not unique to vertebrate biology, multiple annexin orthologs are present in almost all eukaryotes. Their ability to combine either dynamically or constitutively with membrane lipid bilayers is hypothetically the key property that has led to their retention and multiple adaptation in eukaryotic molecular cell biology. Annexin genes are differentially expressed in many cell types but their disparate functions are still being discovered after more than 40 years of international research. A picture is emerging from gene knock down and knock out studies of individual annexins that these are important supporters rather than critical players in organism development and normal cell and tissue function. However, they appear to be highly significant “early responders” toward challenges arising from cell and tissue abiotic or biotic stress. In humans, recent focus has been on involvement of the annexin family for its involvement in diverse pathologies, especially cancer. From what has become an exceedingly broad field of investigation, we have selected four annexins in particular: AnxA1, 2, 5, and 6. Present both within and external to cells, these annexins are currently under intensive investigation in translational research as biomarkers of cellular dysfunction and as potential therapeutic targets for inflammatory conditions, neoplasia, and tissue repair. Annexin expression and release in response to biotic stress appears to be a balancing act. Under‐ or over‐expression in different circumstances appears to damage rather than restore a healthy homeostasis. This review reflects briefly on what is already known of the structures and molecular cell biology of these selected annexins and considers their actual and potential roles in human health and disease.

Inhibition of the membrane repair protein annexin-A2 prevents tumor invasion and metastasis

“…Involvement of annexins in cancer progression has already been reported [ 41 , 42 , 47 , 48 ]. Nevertheless, given the multifunctionality of this protein family, which has been shown to participate in cell growth, proliferation, motility, and lipid/glucose homeostasis [ 47 , 49 ], it is often difficult to decipher which is the main mechanism that may promote tumor invasion and metastasis.…”

The structural properties of full-length annexin A11

“…Several mutations were identified in a thorough screening of a large cohort of familial ALS patients in the non-conserved N-terminus, including the p.D40G and p.G38R variants in the N-terminus ( Smith et al, 2017 ; Teyssou et al, 2021 ). Although unique to ANXA11, the N-terminus contains a motif that is reminiscent of the N-terminus of annexin A1 (ANXA1) ( de Souza Ferreira et al, 2023 ). In this protein, residues 2–26 form a helix and fold back to pack against the core domain in the absence of calcium.…”

Annexin-A5 Overexpression Increases Sensitivity of MCF-7 and MCF-7/ADR Cells to Epirubicin

“…Annexin A5(ANXA5) is a member of the annexin family of proteins and is well-known for its ability to bind to anionic phospholipids in a Ca 2+ - dependent manner 5 . ANXA5 displays several activities including cell membrane repair 6 , anti-coagulation 7 , anti-inflammatory 6 , and immunomodulatory effects 8 . Cancer biology is another area of ANXA5 activity that has been the focus of numerous researches in recent decades 9 .…”