کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8302513 | 1537737 | 2013 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The pseudokinase tribbles homologue-3 plays a crucial role in cannabinoid anticancer action
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کلمات کلیدی
mTORC2ATF-4THCTRIB3MEFmTORC1Tumor xenograftsCB1CB2C/EBP homologous protein - C / EBP پروتئین همولوگΔ9-Tetrahydrocannabinol - Δ9-تتراهیدروکانیابینولAutophagy - اتوفاژیCHOP - تکه کردنApoptosis - خزان یاختهایCancer - سرطانCell signaling - سیگنالینگ سلولیendoplasmic reticulum - شبکه آندوپلاسمی activating transcription factor 4 - فعال کردن عامل رونویسی 4mouse embryonic fibroblast - موش فیبروبلاست جنینیMammalian target of rapamycin complex 2 - هدف پستانداران رپامایسین 2Mammalian target of rapamycin complex 1 - هدف پستانداران مجتمع رپامایسین 1Cannabinoids - کانابینوئیدcannabinoid type-1 receptor - گیرنده نوع 1 کانابینوئیدCannabinoid type-2 receptor - گیرنده نوع 2 کانابینوئید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Î9-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer. This effect relies, at least in part, on the up-regulation of several endoplasmic reticulum stress-related proteins including the pseudokinase tribbles homologue-3 (TRIB3), which leads in turn to the inhibition of the AKT/mTORC1 axis and the subsequent stimulation of autophagy-mediated apoptosis in tumor cells. Here, we took advantage of the use of cells derived from Trib3-deficient mice to investigate the precise mechanisms by which TRIB3 regulates the anti-cancer action of THC. Our data show that RasV12/E1A-transformed embryonic fibroblasts derived from Trib3-deficient mice are resistant to THC-induced cell death. We also show that genetic inactivation of this protein abolishes the ability of THC to inhibit the phosphorylation of AKT and several of its downstream targets, including those involved in the regulation of the AKT/mammalian target of rapamycin complex 1 (mTORC1) axis. Our data support the idea that THC-induced TRIB3 up-regulation inhibits AKT phosphorylation by regulating the accessibility of AKT to its upstream activatory kinase (the mammalian target of rapamycin complex 2; mTORC2). Finally, we found that tumors generated by inoculation of Trib3-deficient cells in nude mice are resistant to THC anticancer action. Altogether, the observations presented here strongly support that TRIB3 plays a crucial role on THC anti-neoplastic activity. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1831, Issue 10, October 2013, Pages 1573-1578
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1831, Issue 10, October 2013, Pages 1573-1578
نویسندگان
MarÃa Salazar, Mar Lorente, Elena GarcÃa-Taboada, Sonia Hernández-Tiedra, David Davila, Sheila E. Francis, Manuel Guzmán, Endre Kiss-Toth, Guillermo Velasco,