TRAF4 is a critical molecule for Akt activation in lung cancer.
TRAF4 is a critical molecule for Akt activation in lung cancer.
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TRAF4 是肺癌中 Akt 激活的关键分子。
DOI：
10.1158/0008-5472.can-13-0913
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发表时间：
2013-12-01
期刊：
影响因子：
11.2
通讯作者：
Dong Z
中科院分区：
文献类型：
--
作者：
Li W;Peng C;Lee MH;Lim D;Zhu F;Fu Y;Yang G;Sheng Y;Xiao L;Dong X;Ma W;Bode AM;Cao Y;Dong Z
TRAF4是一种在某些癌症中过表达的衔接蛋白，但其对肿瘤发生的作用尚不清楚。在肺癌细胞和原发性肺肿瘤中，我们发现TRAF4过表达。RNA干扰介导的TRAF4表达的减弱减弱了这种情况下的恶性表型，对异种移植小鼠模型中的细胞增殖、锚定非依赖性生长和肿瘤发展产生抑制作用。出乎意料的是，我们发现TRAF4而不是Skp2是通过泛素化激活关键细胞存活激酶Akt所必需的。此外，TRAF4通过抑制Akt途径介导的Glut1和HK2的表达来减轻受损的葡萄糖代谢。总的来说，我们的工作表明TRAF4为肺癌的预防和治疗提供了一个候选的分子靶点。
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.