Small GTPase RBJ Mediates Nuclear Entrapment of MEK1/MEK2 in Tumor Progression
Small GTPase RBJ Mediates Nuclear Entrapment of MEK1/MEK2 in Tumor Progression
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DOI：
10.1016/j.ccr.2014.03.009
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发表时间：
2014-05-12
期刊：
影响因子：
50.3
通讯作者：
Cao, Xuetao
中科院分区：
文献类型：
--
作者：
Chen, Taoyong;Yang, Mingjin;Cao, Xuetao
Ras相关的小GTP酶在癌症中起重要作用。然而，RBJ，Ras相关的小GTP酶的第六个亚家族的代表，在肿瘤发生和肿瘤进展中的作用仍然未知。在这里，我们报告说，RBJ是失调的人胃肠道肿瘤，可以促进癌的发生和肿瘤进展，通过核截留的丝裂原活化蛋白/细胞外信号调节激酶（ERK）激酶（MEK）1/MEK 2和活化的ERK 1/ERK 2。核定位RBJ与MEK/ERK相互作用并延长MEK/ERK激活的持续时间。Rbj缺乏消除了MEK 1/MEK 2的核积累，减弱了ERK 1/ERK 2的激活，并削弱了AOM/DSS诱导的结肠癌发生。此外，Rbj敲低抑制已建立的肿瘤的生长。我们的数据表明，RBJ可能是一个致癌Ras相关的小GTdR介导的核积累的活性MEK 1/MEK 2在肿瘤的进展。
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.