Alkylation of the Tumor Suppressor PTEN Activates Akt and β-Catenin Signaling: A Mechanism Linking Inflammation and Oxidative Stress with Cancer
| العنوان: | Alkylation of the Tumor Suppressor PTEN Activates Akt and β-Catenin Signaling: A Mechanism Linking Inflammation and Oxidative Stress with Cancer |
|---|---|
| المؤلفون: | Frank A. Fitzpatrick, Gary S. Coombs, Tracy M. Covey, Kornelia Edes, David M. Virshup |
| المصدر: | PLoS ONE PLoS ONE, Vol 5, Iss 10, p e13545 (2010) |
| بيانات النشر: | Public Library of Science, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Alkylation, Immunology/Innate Immunity, lcsh:Medicine, Inflammation, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, medicine, Biochemistry/Cell Signaling and Trafficking Structures, PTEN, Humans, Prostaglandin a, lcsh:Science, Protein kinase B, Cell Biology/Chemical Biology of the Cell, PI3K/AKT/mTOR pathway, beta Catenin, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, lcsh:R, PTEN Phosphohydrolase, 3. Good health, Enzyme Activation, Oxidative Stress, Biochemistry, Oncology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Phosphorylation, lcsh:Q, Signal transduction, medicine.symptom, Proto-Oncogene Proteins c-akt, Oxidative stress, Research Article, Signal Transduction |
| الوصف: | 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 A(2), Δ12-prostaglandin J(2) and 15-deoxy-Δ-12,14-prostaglandin J(2)) 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bc9683c04d8fff4027a102075701b44cTest http://europepmc.org/articles/PMC2958828Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bc9683c04d8fff4027a102075701b44c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|