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- Title
Annexin A2 Regulates AKT Upon H2O2-Dependent Signaling Activation in Cancer Cells.
- Authors
Castaldo, Stéphanie Anais; Ajime, Tom; Serrão, Gisela; Anastácio, Fábio; Rosa, Joana Teixeira; Giacomantonio, Carman Anthony; Howarth, Alison; Hill, Richard; Madureira, Patrícia Alexandra
- 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.
- Subjects
CALCIUM-binding proteins; CELLULAR signal transduction; EPIDERMAL growth factor; HYDROGEN peroxide; PHOSPHATASES; PHOSPHOPROTEINS; PHOSPHORYLATION; TRANSFERASES; OXIDATIVE stress
- Publication
Cancers, 2019, Vol 11, Issue 4, p492
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers11040492