The role of c-Src in integrin (α6β4) dependent translational control.

The role of c-Src in integrin (α6β4) dependent translational control.
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DOI:
10.1186/1471-2121-14-49
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发表时间:
2013-11-01
期刊:
影响因子:
--
通讯作者:
Chung J
Chung J
中科院分区:
生物3区
文献类型:
--
作者:
Soung YH;Korneeva N;Kim TH;Chung J

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整合素α6β4通过刺激癌症相关基因的转录和翻译而促进癌症进展。我们前期的研究表明α6β4通过激活mTOR途径刺激VEGF等生存因子的翻译起始。然而,需要定义将α6β4与mTOR激活联系起来的立即早期信号传导事件。在目前的研究中,我们证明了c-Src是一种立即早期信号分子,在MDA-MB-435/β4和MDA-MB-231癌细胞中作用于α6β4依赖性mTOR激活和随后VEGF翻译的上游。m7 GTP-琼脂糖凝胶结合试验表明,Src活性是形成eIF 4F复合物所必需的,而eIF 4F复合物是表达α6β4的人癌细胞中Cap依赖性翻译所必需的。总之,我们的研究表明,整合素β4和c-Src激活是导致mTOR激活和VEGF帽依赖性翻译的重要早期信号事件。
Integrin α6β4 contributes to cancer progression by stimulating transcription as well as translation of cancer related genes. Our previous study demonstrated that α6β4 stimulates translation initiation of survival factors such as VEGF by activating mTOR pathway. However, the immediate early signaling events that link α6β4 to mTOR activation needs to be defined. In the current studies, we demonstrated that c-Src is an immediate early signaling molecule that acts upstream of α6β4 dependent mTOR activation and subsequent translation of VEGF in MDA-MB-435/β4 and MDA-MB-231 cancer cells. m7GTP-Sepharose–binding assay revealed that Src activity is required to form eIF4F complex which is necessary for Cap-dependent translation in α6β4 expressing human cancer cells. Overall, our studies suggest that integrin β4 and c-Src activation is important early signaling events to lead mTOR activation and cap-dependent translation of VEGF.
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