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

被引:32
|
作者
Castaldo, Stephanie Anais [1 ,4 ,5 ]
Ajime, Tom [1 ]
Serrao, Gisela [1 ]
Anastacio, Fabio [1 ]
Rosa, Joana Teixeira [1 ]
Giacomantonio, Carman Anthony [2 ]
Howarth, Alison [3 ]
Hill, Richard [1 ,3 ]
Madureira, Patricia Alexandra [1 ,3 ]
机构
[1] Univ Algarve, Ctr Biomed Res CBMR, Bldg 8,Room 2-22, P-8005139 Faro, Portugal
[2] Dalhousie Univ, Dept Med, Halifax, NS B3H 4R2, Canada
[3] Univ Portsmouth, Brain Tumour Res Ctr Excellence, Inst Biomed & Biomol Sci, Portsmouth PO1 2DT, Hants, England
[4] Univ Leuven, VIB Ctr Canc Biol, B-3000 Leuven, Belgium
[5] Univ Leuven, KU Leuven, Dept Oncol, B-3000 Leuven, Belgium
来源
CANCERS | 2019年 / 11卷 / 04期
关键词
ANXA2; PTEN; PI3K/AKT; PRDX2; H2O2-dependent signaling; REDOX REGULATION; PROTEIN; RAS; TRANSPORT;
D O I
10.3390/cancers11040492
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页数:15
相关论文
共 50 条
  • [31] Involvement of Annexin A2 in Serum-MAF Dependent Phagocytic Activation of Macrophages
    Kawakatsu, Kumpei
    Maemura, Misato
    Seta, Yoshika
    Nishikata, Takahito
    ANTICANCER RESEARCH, 2021, 41 (08) : 4089 - 4092
  • [32] SOD2 enhances cell migration and invasion of tongue squamous cell carcinoma via H2O2-dependent Snail signaling
    Wang, Anxun
    Liu, Zhonghua
    Li, Su
    Cai, Yuchen
    Zheng, Chaoxu
    He, Qianting
    Zhou, Xiaofeng
    CANCER RESEARCH, 2012, 72
  • [33] HYPOXANTHINE-XANTHINE OXIDASE INHIBITS VASCULAR ENDOTHELIAL-CELL CA-2+ SIGNALING BY AN H2O2-DEPENDENT MECHANISM
    WESSON, DE
    ELLIOTT, SJ
    CLINICAL RESEARCH, 1993, 41 (02): : A150 - A150
  • [34] Theoretical Study on Chemiluminescence of H2O2-dependent Tetrachloro-1,4-benzoquinone
    Tang, Yi-Qi
    Liu, Ya-Jun
    JOURNAL OF ORGANIC CHEMISTRY, 2020, 85 (14): : 9042 - 9050
  • [35] Exopolysaccharides from Sinorhizobium meliloti Can Protect against H2O2-Dependent Damage
    Lehman, Alisa P.
    Long, Sharon R.
    JOURNAL OF BACTERIOLOGY, 2013, 195 (23) : 5362 - 5369
  • [36] TaCAMTA4 negatively regulates H2O2-dependent wheat leaf rust resistance by activating catalase 1 expression
    Sun, Tianjie
    Ma, Nan
    Jiao, Yuanyuan
    Wang, Qian
    Wang, Qipeng
    Liu, Na
    Chen, Yan
    Han, Shengfang
    Hou, Chunyan
    Wang, Rongna
    Wang, Dongmei
    PLANT PHYSIOLOGY, 2024,
  • [37] Plasmin-Induced Monocyte Activation Requires the Annexin A2 Heterotetramer for Proinflammatory Signaling
    Syrovets, Tatiana
    Laumonnier, Yves
    Pitterle, Kai
    Simmet, Thomas
    INFLAMMATION RESEARCH, 2005, 54 : S99 - S99
  • [38] The H2O2-dependent activity of a fungal lytic polysaccharide monooxygenase investigated with a turbidimetric assay
    Filandr, Frantisek
    Man, Petr
    Halada, Petr
    Chang, Hucheng
    Ludwig, Roland
    Kracher, Daniel
    BIOTECHNOLOGY FOR BIOFUELS, 2020, 13 (01)
  • [39] The H2O2-dependent activity of a fungal lytic polysaccharide monooxygenase investigated with a turbidimetric assay
    Frantisek Filandr
    Petr Man
    Petr Halada
    Hucheng Chang
    Roland Ludwig
    Daniel Kracher
    Biotechnology for Biofuels, 13
  • [40] Nitric oxide mediates inhibition of H2O2-dependent activation of NF-κB and sensitizes tumor cells to TNF-α-mediated cytotoxicity and apoptosis
    Garban, H
    Fukuto, J
    Bonavida, B
    FASEB JOURNAL, 1999, 13 (04): : A610 - A610