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

BMC Cell Biology

Jun Chung³  Tae Hyong Kim²  Nadejda Korneeva¹  Young Hwa Soung³ 

[1] Departments of Emergency Medicine and Biochemistry, Louisiana State University Health Science Center, Shreveport, Louisiana 71130, USA;The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio 43210, USA;Department of Physiology and Stephenson Cancer Center, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA

关键词: VEGF;    mTOR;    Translation;    Integrin;    c-Src;   

Others  :  855078
DOI  :  10.1186/1471-2121-14-49

 received in 2013-06-10, accepted in 2013-10-25,  发布年份 2013

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2013 Soung et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 3.

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