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Annexin A2 is a novel Cellular Redox Regulatory Protein involved in Tumorigenesis

Annexins are a structurally related family of calcium and phospholipid-binding proteins that are involved in the regulation of a wide range of molecular and cellular processes. Annexin A2 is unique among the annexins in that it possesses redox sensitive cysteine(s). The ubiquitous and abundant expre...

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Autores principales: Madureira, Patricia Alexandra, Hill, Richard, Miller, Victoria Ann, Giacomantonio, Carman, Lee, Patrick Wing Kwong, Waisman, David Morton
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282068/
https://www.ncbi.nlm.nih.gov/pubmed/22185818
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author Madureira, Patricia Alexandra
Hill, Richard
Miller, Victoria Ann
Giacomantonio, Carman
Lee, Patrick Wing Kwong
Waisman, David Morton
author_facet Madureira, Patricia Alexandra
Hill, Richard
Miller, Victoria Ann
Giacomantonio, Carman
Lee, Patrick Wing Kwong
Waisman, David Morton
author_sort Madureira, Patricia Alexandra
collection PubMed
description Annexins are a structurally related family of calcium and phospholipid-binding proteins that are involved in the regulation of a wide range of molecular and cellular processes. Annexin A2 is unique among the annexins in that it possesses redox sensitive cysteine(s). The ubiquitous and abundant expression of ANXA2 in cells and its reactivity with hydrogen peroxide led us to hypothesize that this protein could play a role in cellular redox regulation. Here we show that ANXA2 protein levels are induced by hydrogen peroxide. Furthermore, depletion of ANXA2 resulted in the elevation of cellular reactive oxygen species (ROS) upon oxidative stress, increased activation of the ROS-induced pro-apoptotic kinases, JNK, p38 and Akt and elevated sensitivity to ROS-mediated cellular damage/death. ANXA2-null mice showed significantly elevated protein oxidation in the liver and lung tissues compared to WT mice. ANXA2 depleted cancer cells showed enhanced cellular protein oxidationconcomitant with decreased tumor growth compared to control cancer cells andboth the oxidation of cellular proteins and tumor growth deficit werereversed by the antioxidant N-acetyl cysteine, indicating that ANXA2 plays akey role in the regulation of cellular redox during tumorigenesis. Ex-vivo human cancer studies showed that up-regulation of the reduced form of ANXA2 is associated with protection of the tumor proteins from oxidation. In summary, our results indicate that ANXA2 plays an important role incellular redox regulation by protecting cells from oxidative stress, aneffect that is particularly important during tumorigenesis.
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spelling pubmed-32820682012-02-22 Annexin A2 is a novel Cellular Redox Regulatory Protein involved in Tumorigenesis Madureira, Patricia Alexandra Hill, Richard Miller, Victoria Ann Giacomantonio, Carman Lee, Patrick Wing Kwong Waisman, David Morton Oncotarget Research Papers Annexins are a structurally related family of calcium and phospholipid-binding proteins that are involved in the regulation of a wide range of molecular and cellular processes. Annexin A2 is unique among the annexins in that it possesses redox sensitive cysteine(s). The ubiquitous and abundant expression of ANXA2 in cells and its reactivity with hydrogen peroxide led us to hypothesize that this protein could play a role in cellular redox regulation. Here we show that ANXA2 protein levels are induced by hydrogen peroxide. Furthermore, depletion of ANXA2 resulted in the elevation of cellular reactive oxygen species (ROS) upon oxidative stress, increased activation of the ROS-induced pro-apoptotic kinases, JNK, p38 and Akt and elevated sensitivity to ROS-mediated cellular damage/death. ANXA2-null mice showed significantly elevated protein oxidation in the liver and lung tissues compared to WT mice. ANXA2 depleted cancer cells showed enhanced cellular protein oxidationconcomitant with decreased tumor growth compared to control cancer cells andboth the oxidation of cellular proteins and tumor growth deficit werereversed by the antioxidant N-acetyl cysteine, indicating that ANXA2 plays akey role in the regulation of cellular redox during tumorigenesis. Ex-vivo human cancer studies showed that up-regulation of the reduced form of ANXA2 is associated with protection of the tumor proteins from oxidation. In summary, our results indicate that ANXA2 plays an important role incellular redox regulation by protecting cells from oxidative stress, aneffect that is particularly important during tumorigenesis. Impact Journals LLC 2011-12-20 /pmc/articles/PMC3282068/ /pubmed/22185818 Text en Copyright: © 2011 Madureira et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Research Papers
Madureira, Patricia Alexandra
Hill, Richard
Miller, Victoria Ann
Giacomantonio, Carman
Lee, Patrick Wing Kwong
Waisman, David Morton
Annexin A2 is a novel Cellular Redox Regulatory Protein involved in Tumorigenesis
title Annexin A2 is a novel Cellular Redox Regulatory Protein involved in Tumorigenesis
title_full Annexin A2 is a novel Cellular Redox Regulatory Protein involved in Tumorigenesis
title_fullStr Annexin A2 is a novel Cellular Redox Regulatory Protein involved in Tumorigenesis
title_full_unstemmed Annexin A2 is a novel Cellular Redox Regulatory Protein involved in Tumorigenesis
title_short Annexin A2 is a novel Cellular Redox Regulatory Protein involved in Tumorigenesis
title_sort annexin a2 is a novel cellular redox regulatory protein involved in tumorigenesis
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282068/
https://www.ncbi.nlm.nih.gov/pubmed/22185818
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