Annexin A1 localization and its relevance to cancer

2016 ◽  
Vol 130 (4) ◽  
pp. 205-220 ◽  
Author(s):  
Zied Boudhraa ◽  
Bernadette Bouchon ◽  
Claire Viallard ◽  
Michel D'Incan ◽  
Françoise Degoul
Keyword(s):  
Cancer Progression ◽  
Formyl Peptide Receptor ◽  
Annexin A1 ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Cell Compartments ◽  
Oncogenic Pathways ◽  
Formyl Peptide ◽  
Cell Processes ◽  
Inflammation Resolution

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.

scholarly journals Formyl Peptide Receptors and Annexin A1: Complementary Mechanisms to Infliximab in Murine Experimental Colitis and Crohn’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Marina de Paula-Silva ◽  
Gustavo Henrique Oliveira da Rocha ◽  
Milena Fronza Broering ◽  
Maria Luíza Queiroz ◽  
Silvana Sandri ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Formyl Peptide Receptor ◽  
Annexin A1 ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
Inflammatory Bowel

Non-responsiveness to anti-TNF-α therapies presents relevant rates in inflammatory bowel disease patients, presenting the need to find biomarkers involved in therapeutic efficacy. Herein, we demonstrate that higher levels of colonic formyl peptide receptor 1 and annexin A1 correlate with histological recovery in Crohn’s disease patients under remission. Using the dextran sulfate sodium colitis model in mice, we suggest that infliximab induces annexin A1 expression and secretion in activated intestinal leukocytes. Conversely, this mechanism might stimulate epithelial formyl peptide receptors, inducing wound healing and consequent histological remission. Our data indicate that assessing intestinal expressions of formyl peptide receptors and annexin A1 might provide precious information on the disease activity and responsiveness to infliximab in inflammatory bowel disease patients.

scholarly journals Formyl-Peptide Receptor Activation Enhances Phagocytosis of Community-Acquired Methicillin-Resistant Staphylococcus aureus

2019 ◽  
Author(s):  
Elisabeth Weiß ◽  
Katja Schlatterer ◽  
Christian Beck ◽  
Andreas Peschel ◽  
Dorothee Kretschmer
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Receptor Activation ◽  
Formyl Peptide Receptor ◽  
Peptide Receptors ◽  
Highly Pathogenic ◽  
Methicillin Resistant ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
First Time

Abstract Background Formyl-peptide receptors (FPRs) are important pattern recognition receptors that sense specific bacterial peptides. Formyl-peptide receptors are highly expressed on neutrophils and monocytes, and their activation promotes the migration of phagocytes to sites of infection. It is currently unknown whether FPRs may also influence subsequent processes such as bacterial phagocytosis and killing. Staphylococcus aureus, especially highly pathogenic community-acquired methicillin-resistant S aureus strains, release high amounts of FPR2 ligands, the phenol-soluble modulins. Methods We demonstrate that FPR activation leads to upregulation of complement receptors 1 and 3 as well as FCγ receptor I on neutrophils and, consequently, increased opsonic phagocytosis of S aureus and other pathogens. Results Increased phagocytosis promotes killing of S aureus and interleukin-8 release by neutrophils. Conclusions We show here for the first time that FPRs govern opsonic phagocytosis. Manipulation of FPR2 activation could open new therapeutic opportunities against bacterial pathogens.

N-Formyl Peptide Receptors Display an Asymmetric Distribution In Migrating Human Neutrophils

1999 ◽  
Vol 5 (S2) ◽  
pp. 1126-1127
Author(s):  
Vesa-Matti Loitto ◽  
Birgitta Rasmusson ◽  
Karl-Eric Magnusson
Keyword(s):  
Cell Movement ◽  
Ccd Camera ◽  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Asymmetric Distribution ◽  
Phagocytic Cells ◽  
Peptide Receptors ◽  
Directed Movement ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide

A debated and yet unanswered question, in regard to polarization and directed movement of phagocytic cells, concerns the distribution of chemoattractant receptors during cell locomotion1. We have therefore studied the instantaneous distribution of N-formyl-peptide receptors on living neutrophils. Using a fluorescent N-formyl-peptide receptor antagonist, tert-butyloxycarbonyl-Phe(D)-Leu-Phe(D)-Leu-Phe-OH (Boc-FLFLF), and a fluorescent receptor agonist, formyl-Nle-Leu-Phe-Nle-Tyr-Lys (fnLLFnLYK), the localization of the chemoattractant receptors could be followed during random migratio2. Neutrophils were adhered to plasma-coated coverslips. A Nomarski differential interference contrast (DIC)- image was taken, and rapidly followed by a fluorescence-image captured with a water-cooled, slow-scan CCD-camera. Then a second DIC-image was directly recorded to reveal the direction of cell movement.Using fnLLFnLYK we observed that the distribution of N-formyl-peptide receptors was clearly heterogeneous as shown in figure. Fluorescence was concentrated mainly at the rear and front of elongated locomoting cells, leaving the cell body almost non-fluorescent.

scholarly journals Annexin A1 Released in Extracellular Vesicles by Pancreatic Cancer Cells Activates Components of the Tumor Microenvironment, through Interaction with the Formyl-Peptide Receptors

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2719
Author(s):  
Nunzia Novizio ◽  
Raffaella Belvedere ◽  
Emanuela Pessolano ◽  
Alessandra Tosco ◽  
Amalia Porta ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Soluble Form ◽  
Annexin A1 ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Pancreatic Cancer Cells ◽  
Formyl Peptide

Pancreatic cancer (PC) is one of the most aggressive cancers in the world. Several extracellular factors are involved in its development and metastasis to distant organs. In PC, the protein Annexin A1 (ANXA1) appears to be overexpressed and may be identified as an oncogenic factor, also because it is a component in tumor-deriving extracellular vesicles (EVs). Indeed, these microvesicles are known to nourish the tumor microenvironment. Once we evaluated the autocrine role of ANXA1-containing EVs on PC MIA PaCa-2 cells and their pro-angiogenic action, we investigated the ANXA1 paracrine effect on stromal cells like fibroblasts and endothelial ones. Concerning the analysis of fibroblasts, cell migration/invasion, cytoskeleton remodeling, and the different expression of specific protein markers, all features of the cell switching into myofibroblasts, were assessed after administration of wild type more than ANXA1 Knock-Out EVs. Interestingly, we demonstrated a mechanism by which the ANXA1-EVs complex can stimulate the activation of formyl peptide receptors (FPRs), triggering mesenchymal switches and cell motility on both fibroblasts and endothelial cells. Therefore, we highlighted the importance of ANXA1/EVs-FPR axes in PC progression as a vehicle of intercommunication tumor cells-stroma, suggesting a specific potential prognostic/diagnostic role of ANXA1, whether in soluble form or even if EVs are captured in PC.

scholarly journals Formyl peptide receptors and the regulation of ACTH secretion: targets for annexin A1, lipoxins, and bacterial peptides

2007 ◽  
Vol 21 (4) ◽  
pp. 1037-1046 ◽  
Author(s):  
C. D. John ◽  
V. Sahni ◽  
D. Mehet ◽  
J. F. Morris ◽  
H. C. Christian ◽  
...  
Keyword(s):  
Annexin A1 ◽  
Acth Secretion ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide

scholarly journals N-formyl peptide receptors in human neutrophils display distinct membrane distribution and lateral mobility when labeled with agonist and antagonist.

1993 ◽  
Vol 121 (6) ◽  
pp. 1281-1289 ◽  
Author(s):  
B Johansson ◽  
M P Wymann ◽  
K Holmgren-Peterson ◽  
K E Magnusson
Keyword(s):  
Confocal Microscopy ◽  
Lateral Diffusion ◽  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Lateral Mobility ◽  
Peptide Receptors ◽  
Tetrazolium Chloride ◽  
Formyl Peptide Receptors ◽  
Peptide Receptor ◽  
Formyl Peptide

Receptors for bacterial N-formyl peptides are instrumental for neutrophil chemotactic locomotion and activation at sites of infection. As regulatory mechanisms for signal transduction, both rapid coupling of the occupied receptor to cytoskeletal components, and receptor lateral redistribution, have been suggested (Jesaitis et al., 1986, 1989). To compare the distribution and lateral diffusion of the nonactivated and activated neutrophil N-formyl-peptide receptor, before internalization, we used a new fluorescent N-formyl-peptide receptor antagonist, tertbutyloxycarbonyl-Phe(D)-Leu-Phe(D)-Leu-Phe-OH (Boc-FLFLF, 0.1-1 microM), and the fluorescent receptor agonist formyl-Nle-Leu-Phe-Nle-Tyr-Lys (fnLLFnLYK, 0.1-1 microM). Fluorescent Boc-FLFLF did not elicit an oxidative burst in the neutrophil at 37 degrees C, as assessed by chemiluminescence and reduction of p-nitroblue tetrazolium chloride, but competed efficiently both with formyl-methionyl-leucyl-phenylalanine (fMLF) and fnLLFnLYK. It was not internalized, as evidenced by confocal microscopy and acid elution of surface bound ligand. The lateral mobility characteristics of the neutrophil fMLF receptor were investigated with the technique of FRAP. The diffusion coefficient (D) was similar for antagonist- and agonist-labeled receptors (D approximately 5 x 10(-10) cm2/s), but the fraction of mobile receptors was significantly lower in agonist- compared to antagonist-labeled cells, approximately 40% in contrast to approximately 60%. This reduction in receptor mobile fraction was slightly counteracted, albeit not significantly, by dihydrocytochalasin B (dhcB, 5 microM). To block internalization of agonist-labeled receptors, receptor mobility measurements were done at 14 degrees C. At this temperature, confocal microscopy revealed clustering of receptors in response to agonist binding, compared to a more uniform receptor distribution in antagonist-labeled cells. The pattern of agonist-induced receptor clustering was less apparent after dhcB treatment. To summarize, this work shows that activated N-formyl peptide receptors aggregate and immobilize in the plane of the neutrophil plasma membrane before internalization, a process that is affected, but not significantly reversed, by cytochalasin. The results are consistent with a model where arrested receptors are associated mainly with a cytochalasin-insensitive pool of cytoskeletal elements.

scholarly journals A long-lived peptide-conjugated iridium(iii) complex as a luminescent probe and inhibitor of the cell migration mediator, formyl peptide receptor 2

2018 ◽  
Vol 9 (43) ◽  
pp. 8171-8177 ◽  
Author(s):  
Kasipandi Vellaisamy ◽  
Guodong Li ◽  
Wanhe Wang ◽  
Chung-Hang Leung ◽  
Dik-Lung Ma
Keyword(s):  
Cell Migration ◽  
Wound Repair ◽  
Inflammatory Diseases ◽  
Formyl Peptide Receptor ◽  
Luminescent Probe ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Peptide Receptor ◽  
Formyl Peptide

Formyl peptide receptors play important biological and therapeutic roles in wound repair and inflammatory diseases.

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