Deregulated Myc Requires MondoA/Mlx for Metabolic Reprogramming and Tumorigenesis

被引：172

作者：

Carroll, Patrick A. ^{[1
]}

Diolaiti, Daniel ^{[1
]}

McFerrin, Lisa ^{[1
]}

Gu, Haiwei ^{[2
]}

Djukovic, Danijel ^{[2
]}

Du, Jianhai ^{[4
]}

Cheng, Pei Feng ^{[1
]}

Anderson, Sarah ^{[1
]}

Ulrich, Michelle ^{[1
]}

Hurley, James B. ^{[4
,5
]}

Raftery, Daniel ^{[2
,3
]}

Ayer, Donald E. ^{[6
]}

Eisenman, Robert N. ^{[1
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA

[2] Univ Washington, Dept Anesthesiol & Pain Med, Northwest Metabol Res Ctr, Seattle, WA 98109 USA

[3] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA

[4] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[5] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA

[6] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA

来源：

CANCER CELL | 2015年 / 27卷 / 02期

关键词：

C-MYC; CELL-PROLIFERATION; GLUTAMINE; NEUROBLASTOMA; MAX; EXPRESSION; MLX; INDUCTION; APOPTOSIS; PROTEIN;

D O I：

10.1016/j.ccell.2014.11.024

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Deregulated Myc transcriptionally reprograms cell metabolism to promote neoplasia. Here we show that oncogenic Myc requires the Myc superiamily member MondoA, a nutrient-sensing transcription factor, for tumorigenesis. Knockdown of MondoA, or its dimerization partner Mlx, blocks Myc-induced reprogramming of multiple metabolic pathways, resulting in apoptosis. Identification and knockdown of genes coregulated by Myc and MondoA have allowed us to define metabolic functions required by deregulated Myc and demonstrate a critical role for lipid biosynthesis in survival of Myc-driven cancer. Furthermore, overexpression of a subset of Myc and MondoA coregulated genes correlates with poor outcome of patients with diverse cancers. Coregulation of cancer metabolism by Myc and MondoA provides the potential for therapeutics aimed at inhibiting MondoA and its target genes.

引用

页码：271 / 285

页数：15

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