Small GTPase RBJ Mediates Nuclear Entrapment of MEK1/MEK2 in Tumor Progression

被引：42

作者：

Chen, Taoyong ^{[1
,2
,3
,4
]}

Yang, Mingjin ^{[1
,2
,3
,4
]}

Yu, Zhou ^{[5
]}

Tang, Songqing ^{[5
]}

Wang, Chen ^{[1
,2
]}

Zhu, Xuhui ^{[1
,2
]}

Guo, Jun ^{[1
,2
]}

Li, Nan ^{[1
,2
]}

Zhang, Weiping ^{[1
,2
]}

Hou, Jin ^{[1
,2
]}

Liu, Haibo ^{[1
,2
]}

Han, Chaofeng ^{[1
,2
]}

Liu, Qiuyan ^{[1
,2
]}

Gu, Yan ^{[1
,2
]}

Qian, Cheng ^{[1
,2
]}

Wan, Tao ^{[1
,2
]}

Cui, Long ^{[6
]}

Zhu, Minghua ^{[7
]}

Zheng, Weiqiang ^{[7
]}

Cao, Xuetao ^{[1
,2
,3
,4
,5
]}

机构：

[1] Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R China

[2] Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

[3] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Key Lab Med Mol Biol, Beijing 100005, Peoples R China

[4] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Immunol, Beijing 100005, Peoples R China

[5] Zhejiang Univ, Sch Med, Inst Immunol, Hangzhou 310058, Zhejiang, Peoples R China

[6] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Colorectal Surg, Sch Med, Shanghai 200092, Peoples R China

[7] Second Mil Med Univ, Changhai Hosp, Dept Pathol, Shanghai 200433, Peoples R China

来源：

CANCER CELL | 2014年 / 25卷 / 05期

基金：

中国国家自然科学基金;

关键词：

ACTIVATED PROTEIN-KINASE; MAP KINASE; METASTATIC MELANOMA; EXPORT SIGNAL; K-RAS; CANCER; CELLS; TRANSFORMATION; MECHANISMS; ERK;

D O I：

10.1016/j.ccr.2014.03.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ras-related small GTPases play important roles in cancer. However, the roles of RBJ, a representative of the sixth subfamily of Ras-related small GTPases, in tumorigenesis and tumor progression remain unknown. Here, we report that RBJ is dysregulated in human gastrointestinal cancers and can promote carcinogenesis and tumor progression via nuclear entrapment of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/MEK2 and activation of ERK1/ERK2. Nucleus-localized RBJ interacts with MEK/ERK and prolongs the duration of MEK/ERK activation. Rbj deficiency abrogates nuclear accumulation of MEK1/MEK2, attenuates ERK1/ERK2 activation, and impairs AOM/DSS-induced colonic carcinogenesis. Moreover, Rbj knockdown inhibits growth of established tumors. Our data suggest that RBJ may be an oncogenic Ras-related small GTPase mediating nuclear accumulation of active MEK1/MEK2 in tumor progression.

引用

页码：682 / 696

页数：15

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