TRAF4 Is a Critical Molecule for Akt Activation in Lung Cancer

被引：91

作者：

Li, Wei ^{[1
,2
]}

Peng, Cong ^{[1
,3
]}

Lee, Mee-Hyun ^{[1
]}

Lim, DoYoung ^{[1
]}

Zhu, Feng ^{[1
]}

Fu, Yang ^{[1
,4
]}

Yang, Ge ^{[1
,4
,5
]}

Sheng, Yuqiao ^{[1
,4
,5
]}

Xiao, Lanbo ^{[2
]}

Dong, Xin ^{[2
]}

Ma, WeiYa ^{[1
]}

Bode, Ann M. ^{[1
]}

Cao, Ya ^{[2
]}

Dong, Zigang ^{[1
]}

机构：

[1] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA

[2] Xiangya Sch Med, Canc Res Inst, Changsha, Hunan, Peoples R China

[3] Cent S Univ, Xiangya Hosp, Changsha, Hunan, Peoples R China

[4] Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China

[5] Zhengzhou Univ, Basic Med Sch, Zhengzhou 450052, Henan, Peoples R China

来源：

CANCER RESEARCH | 2013年 / 73卷 / 23期

基金：

中国国家自然科学基金; 国家高技术研究发展计划(863计划);

关键词：

PROTEIN; FAMILY; IDENTIFICATION; UBIQUITINATION; SURVIVAL; PATHWAY;

D O I：

10.1158/0008-5472.CAN-13-0913

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

TRAF4 is an adapter protein overexpressed in certain cancers, but its contributions to tumorigenesis are unclear. In lung cancer cells and primary lung tumors, we found that TRAF4 is overexpressed. RNA interference-mediated attenuation of TRAF4 expression blunted the malignant phenotype in this setting, exerting inhibitory effects on cell proliferation, anchorage-independent growth, and tumor development in a xenograft mouse model. Unexpectedly, we discovered that TRAF4, but not Skp2, was required for activation of the pivotal cell survival kinase Akt through ubiquitination. Furthermore, TRAF4 attenuation impaired glucose metabolism by inhibiting expression of Glut1 and HK2 mediated by the Akt pathway. Overall, our work suggests that TRAF4 offers a candidate molecular target for lung cancer prevention and therapy. (C)2013 AACR.

引用

页码：6938 / 6950

页数：13

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