期刊
CANCERS
卷 11, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/cancers11040492
关键词
ANXA2; PTEN; PI3K/AKT; PRDX2; H2O2-dependent signaling
类别
资金
- FCT Investigator contract from the Foundation for Science and Technology (FCT), Portugal [IF/00614/2014]
- FCT exploratory grant [IF/00614/2014/CP12340006]
- FCT Research Center Grant [UID/BIM/04773/2013CBMR1334]
- FCT research fellowship [WELCOMEII/57/UALG/1050/2011]
- ERASMUS Mundus fellowship (EMQAL) [FPAnr2013-0225]
- Ollie Young Foundation [1148511]
- Brain Tumour Research
- Fundação para a Ciência e a Tecnologia [WELCOMEII/57/UALG/1050/2011] Funding Source: FCT
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.
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