دورية أكاديمية
Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached
| العنوان: | Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached |
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| المؤلفون: | Wilcock, Daniel J, Badrock, Andrew P, Wong, Chun W, Owen, Rhys, Guerin, Melissa, Southam, Andrew D, Johnston, Hannah, Telfer, Brian A, Fullwood, Paul, Watson, Joanne, Ferguson, Harriet, Ferguson, Jennifer, Lloyd, Gavin R, Jankevics, Andris, Dunn, Warwick B, Wellbrock, Claudia, Lorigan, Paul, Ceol, Craig J, Francavilla, Chiara, Smith, Michael P, Hurlstone, Adam F L |
| المساهمون: | Molecular, Cell and Cancer Biology, Program in Molecular Medicine |
| المصدر: | Cell reports ; 39 ; 12 ; 110995 ; United Kingdom ; United States |
| سنة النشر: | 2023 |
| المجموعة: | University of Massachusetts, Medical School: eScholarship@UMMS |
| مصطلحات موضوعية: | CP: Cancer, DGAT1, SOD1, fatty acids, lipid droplets, melanoma, oxidative stress, reactive oxygen species |
| الوصف: | Dysregulated cellular metabolism is a cancer hallmark for which few druggable oncoprotein targets have been identified. Increased fatty acid (FA) acquisition allows cancer cells to meet their heightened membrane biogenesis, bioenergy, and signaling needs. Excess FAs are toxic to non-transformed cells but surprisingly not to cancer cells. Molecules underlying this cancer adaptation may provide alternative drug targets. Here, we demonstrate that diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral to triacylglyceride synthesis and lipid droplet formation, is frequently up-regulated in melanoma, allowing melanoma cells to tolerate excess FA. DGAT1 over-expression alone transforms p53-mutant zebrafish melanocytes and co-operates with oncogenic BRAF or NRAS for more rapid melanoma formation. Antagonism of DGAT1 induces oxidative stress in melanoma cells, which adapt by up-regulating cellular reactive oxygen species defenses. We show that inhibiting both DGAT1 and superoxide dismutase 1 profoundly suppress tumor growth through eliciting intolerable oxidative stress. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2211-1247 |
| العلاقة: | Cell Reports; https://doi.org/10.1016/j.celrep.2022.110995Test; Wilcock DJ, Badrock AP, Wong CW, Owen R, Guerin M, Southam AD, Johnston H, Telfer BA, Fullwood P, Watson J, Ferguson H, Ferguson J, Lloyd GR, Jankevics A, Dunn WB, Wellbrock C, Lorigan P, Ceol C, Francavilla C, Smith MP, Hurlstone AFL. Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached. Cell Rep. 2022 Jun 21;39(12):110995. doi:10.1016/j.celrep.2022.110995. PMID: 35732120; PMCID: PMC9638004.; http://hdl.handle.net/20.500.14038/52673Test |
| DOI: | 10.1016/j.celrep.2022.110995 |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2022.110995Test https://doi.org/20.500.14038/52673Test https://hdl.handle.net/20.500.14038/52673Test |
| حقوق: | Copyright 2022 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0Test/). ; Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.26E93A4B |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 22111247 |
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| DOI: | 10.1016/j.celrep.2022.110995 |