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DOI | 10.1038/s41467-018-03647-5 |
Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy | |
Talebi, Ali1; Dehairs, Jonas1; Rambow, Florian2,3; Rogiers, Aljosja2,3; Nittner, David4,5; Derua, Rita6; Vanderhoydonc, Frank1; Duarte, Joao A. G.7,8; Bosisio, Francesca9,10; Van den Eynde, Kathleen9,10; Nys, Kris11; Perez, Monica Vara11; Agostinis, Patrizia11; Waelkens, Etienne6; Van den Oord, Joost9,10; Fendt, Sarah-Maria7,8; Marine, Jean-Christophe2,3; Swinnen, Johannes V.1 | |
2018-06-27 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Belgium |
英文摘要 | Whereas significant anti-tumor responses are observed in most BRAF(V600E)-mutant melanoma patients exposed to MAPK-targeting agents, resistance almost invariably develops. Here, we show that in therapy-responsive cells BRAF inhibition induces downregulation of the processing of Sterol Regulator Element Binding (SREBP-1) and thereby lipogenesis. Irrespective of the escape mechanism, therapy-resistant cells invariably restore this process to promote lipid saturation and protect melanoma from ROS-induced damage and lipid peroxidation. Importantly, pharmacological SREBP-1 inhibition sensitizes BRAFV600E-mutant therapy-resistant melanoma to BRAF(V600E) inhibitors both in vitro and in a pre-clinical PDX in vivo model. Together, these data indicate that targeting SREBP-1-induced lipogenesis may offer a new avenue to overcome acquisition of resistance to BRAF-targeted therapy. This work also provides evidence that targeting vulnerabilities downstream of oncogenic signaling offers new possibilities in overcoming resistance to targeted therapies. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000436540700018 |
WOS关键词 | FATTY-ACID SYNTHASE ; ELEMENT-BINDING PROTEINS ; PROSTATE-CANCER ; GENE-EXPRESSION ; SMALL-MOLECULE ; CELLS ; MELANOMA ; ACTIVATION ; SREBP ; RAF |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203735 |
专题 | 资源环境科学 |
作者单位 | 1.Katholieke Univ Leuven, Dept Oncol, Lab Lipid Metab & Canc, LKI Leuven Canc Inst, B-3000 Leuven, Belgium; 2.VIB Ctr Canc Biol, Lab Mol Canc Biol, B-3000 Leuven, Belgium; 3.Katholieke Univ Leuven, Lab Mol Canc Biol, Dept Oncol, B-3000 Leuven, Belgium; 4.VIB KU Leuven Ctr Canc Biol, Histopathol Expertise Ctr, B-3000 Leuven, Belgium; 5.Katholieke Univ Leuven, Dept Oncol, B-3000 Leuven, Belgium; 6.Katholieke Univ Leuven, Lab Prot Phosphorylat & Prote, Dept Cellular & Mol Med, B-3000 Leuven, Belgium; 7.Katholieke Univ Leuven, Dept Oncol, Lab Cellular Metab & Metab Regulat, LKI Leuven Canc Inst, B-3000 Leuven, Belgium; 8.VIB Ctr Canc Biol, Lab Cellular Metab & Metab Regulat, B-3000 Leuven, Belgium; 9.Katholieke Univ Leuven, Translat Cell & Tissue Res, Dept Imaging & Pathol, Leuven, Belgium; 10.UZ Leuven, Dept Pathol, B-3000 Leuven, Belgium; 11.Katholieke Univ Leuven, Lab Cell Death Res & Therapy, Dept Cellular & Mol Med, B-3000 Leuven, Belgium |
推荐引用方式 GB/T 7714 | Talebi, Ali,Dehairs, Jonas,Rambow, Florian,et al. Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Talebi, Ali.,Dehairs, Jonas.,Rambow, Florian.,Rogiers, Aljosja.,Nittner, David.,...&Swinnen, Johannes V..(2018).Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy.NATURE COMMUNICATIONS,9. |
MLA | Talebi, Ali,et al."Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy".NATURE COMMUNICATIONS 9(2018). |
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