Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0013545
Title: Alkylation of the tumor suppressor PTEN activates Akt and β-catenin signaling: A mechanism linking inflammation and oxidative stress with cancer
Authors: Covey, T.M. 
Edes, K.
Coombs, G.S. 
Virshup, D.M. 
Fitzpatrick, F.A.
Issue Date: 2010
Citation: Covey, T.M., Edes, K., Coombs, G.S., Virshup, D.M., Fitzpatrick, F.A. (2010). Alkylation of the tumor suppressor PTEN activates Akt and β-catenin signaling: A mechanism linking inflammation and oxidative stress with cancer. PLoS ONE 5 (10) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0013545
Abstract: PTEN, a phosphoinositide-3-phosphatase, serves dual roles as a tumor suppressor and regulator of cellular anabolic/catabolic metabolism. Adaptation of a redox-sensitive cysteinyl thiol in PTEN for signal transduction by hydrogen peroxide may have superimposed a vulnerability to other mediators of oxidative stress and inflammation, especially reactive carbonyl species, which are commonly occurring by-products of arachidonic acid peroxidation. Using MCF7 and HEK-293 cells, we report that several reactive aldehydes and ketones, e.g. electrophilic α,β-enals (acrolein, 4-hydroxy-2-nonenal) and α,β- enones (prostaglandin A2, Δ12-prostaglandin J2 and 15-deoxy-Δ-12,14-prostaglandin J2) covalently modify and inactivate cellular PTEN, with ensuing activation of PKB/Akt kinase; phosphorylation of Akt substrates; increased cell proliferation; and increased nuclear β-catenin signaling. Alkylation of PTEN by α,β-enals/enones and interference with its restraint of cellular PKB/Akt signaling may accentuate hyperplastic and neoplastic disorders associated with chronic inflammation, oxidative stress, or aging. © 2010 Covey et al.
Source Title: PLoS ONE
URI: http://scholarbank.nus.edu.sg/handle/10635/124645
ISSN: 19326203
DOI: 10.1371/journal.pone.0013545
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