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Annexin A2 Regulates AKT Upon H2O2-Dependent Signaling Activation in Cancer Cells

1
Centre for Biomedical Research (CBMR), Campus of Gambelas, University of Algarve, Building 8, Room 2.22, 8005-139 Faro, Portugal
2
Department of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada
3
Brain Tumour Research Centre of Excellence, Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, PO1 2DT Portsmouth, UK
*
Author to whom correspondence should be addressed.
Current Address: VIB Center for Cancer Biology and KU Leuven Department of Oncology, University of Leuven, 3000 Leuven, Belgium.
Cancers 2019, 11(4), 492; https://doi.org/10.3390/cancers11040492
Received: 14 March 2019 / Revised: 31 March 2019 / Accepted: 3 April 2019 / Published: 7 April 2019
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Abstract

Hydrogen peroxide (H2O2) is a main second messenger in oncogenic signaling networks including the Ras and the growth factor receptor pathways. This is achieved predominantly through the oxidation of redox-sensitive cysteine (Cys) residues in proteins resulting in changes to their structure and function. We previously identified annexin A2 (ANXA2) as a redox regulatory protein that plays an important cellular role during oxidative stress and also promoting tumorigenesis. Here we investigated the role of ANXA2 in the regulation of H2O2-dependent signaling that drives tumor progression. We show that depletion of ANXA2 leads to the enhanced activation of AKT following either EGF/EGFR stimulation or oncogenic Ras transformation. The phosphatase and tensin homologue (PTEN) protein negatively regulates the PI3K/AKT pathway. We demonstrate that ANXA2 via its reactive Cys-8 residue, binds to PTEN and that the co-expression of PTEN and ANXA2, but not ANXA2 Cys-8-Ala mutant, inhibits AKT phosphorylation on Ser 473. These results indicate that ANXA2 is important for PTEN regulation within the PI3K/AKT signaling cascade. Furthermore, we also reveal that ANXA2 inversely regulates the expression of the peroxidase, peroxiredoxin 2, in a reactive oxygen species dependent manner. View Full-Text
Keywords: ANXA2; PTEN; PI3K/AKT; PRDX2; H2O2-dependent signaling ANXA2; PTEN; PI3K/AKT; PRDX2; H2O2-dependent signaling
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Castaldo, S.A.; Ajime, T.; Serrão, G.; Anastácio, F.; Rosa, J.T.; Giacomantonio, C.A.; Howarth, A.; Hill, R.; Madureira, P.A. Annexin A2 Regulates AKT Upon H2O2-Dependent Signaling Activation in Cancer Cells. Cancers 2019, 11, 492.

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