Ect2-Dependent rRNA Synthesis Is Required for KRAS-TRP53-Driven Lung Adenocarcinoma

被引：105

作者：

Justilien, Verline ^{[1
]}

Ali, Syed A. ^{[1
]}

Jamieson, Lee ^{[1
]}

Yin, Ning ^{[1
]}

Cox, Adrienne D. ^{[2
]}

Der, Channing J. ^{[2
]}

Murray, Nicole R. ^{[1
]}

Fields, Alan P. ^{[1
]}

机构：

[1] Mayo Clin, Ctr Comprehens Canc, Dept Canc Biol, Griffin Canc Res Bldg,Room 212,4500 San Pablo Rd, Jacksonville, FL 32224 USA

[2] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

来源：

CANCER CELL | 2017年 / 31卷 / 02期

关键词：

RHO GTPASES; TRANSFORMED GROWTH; ECT2; PROTEIN; CYTOKINESIS; EXPRESSION; DRIVES; GENE; TRANSCRIPTION; POPULATION;

D O I：

10.1016/j.ccell.2016.12.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The guanine nucleotide exchange factor (GEF) epithelial cell transforming sequence 2 (Ect2) has been implicated in cancer. However, it is not clear how Ect2 causes transformation and whether Ect2 is necessary for tumorigenesis in vivo. Here, we demonstrate that nuclear Ect2 GEF activity is required for Kras-Trp53 lung tumorigenesis in vivo and that Ect2-mediated transformation requires Ect2-dependent rDNA transcription. Ect2 activates rRNA synthesis by binding the nucleolar transcription factor upstream binding factor 1 (UBF1) on rDNA promoters and recruiting Rac1 and its downstream effector nucleophosmin (NPM) to rDNA. Protein kinase CL (PKCL)-mediated Ect2 phosphorylation stimulates Ect2-dependent rDNA transcription. Thus, Ect2 regulates rRNA synthesis through a PKCL-Ect2-Rac1-NPM signaling axis that is required for lung tumorigenesis.

引用

页码：256 / 269

页数：14

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