Reduction of Akt2 expression inhibits chemotaxis signal transduction in human breast cancer cells
文献类型：期刊论文
| 作者 | Wang, Jingna2,3; Wan, Wuzhou2,3; Sun, Ronghua2,3; Liu, Ying2,3; Sun, Xiangjun6; Ma, Dalong5; Zhang, Ning1,4 |
| 刊名 | CELLULAR SIGNALLING
 |
| 出版日期 | 2008-06-01 |
| 卷号 | 20期号:6页码:1025-1034 |
| 关键词 | Akt2 Chemotaxis Metastasis Pkc Xi Egf |
| ISSN号 | 0898-6568 |
| DOI | 10.1016/j.cellsig.2007.12.023 |
| 英文摘要 | Protein kinase C xi PKC xi mediates cancer cell chemotaxis by regulating cytoskeleton rearrangement and cell adhesion. In the research for its upstream regulator, we investigated the role of Akt2 in chemotaxis and metastasis of human breast cancer cells. Reduction of Akt2 expression by siRNA inhibited chemotaxis of MDA-MB-231, T47D, and MCF7 cells, three representative human breast cancer cells. Expression of a wild type Akt2 in siRNA transfected cells rescued the phenotype. EGF-induced integrin beta 1 phosphorylation was dampened, consistent with defects in adhesion. Phosphorylation of LIMK and cofilin, a critical step of cofilin recycle and actin polymerization, was also impaired. Thus, Akt2 regulates both cell adhesion and cytoskeleton rearrangement during chemotaxis. Depletion of Akt2 by siRNA impaired the activation of PKC xi while inhibition of PKC xi did not interfere with EGF induced phosphorylation of Akt. Furthermore, EGF induced co-immunoprecipitation between PKC xi and Akt2, but not Akt1, suggesting that a direct interaction between PKC xi and Akt2 in chemotaxis. Protein levels of integrin beta 1, LIMK, cofilin, and PKC xi didn't alter, suggesting that Akt2 does not regulate the expression of these signaling molecules. In a Severe Combine Immunodeficiency mouse model, Akt2 depleted MDA-MB-231 cells showed a marked reduction in metastasis to mouse lungs, demonstrating the biological relevancy of Akt2 in cancer metastasis in vivo. Taken together, our results suggest that Akt2 directly mediates EGF-induced chemotactic signaling pathways through PKC xi and its expression is critical during the extravasation of circulating cancer cells. (C) 2008 Elsevier Inc. All rights reserved. |
| 语种 | 英语 |
| WOS记录号 | WOS:000256238600004 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/63809]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Zhang, Ning |
| 作者单位 | 1.Tianjin Med Univ, Canc Inst & Hosp, Tianjin 300060, Peoples R China 2.Peking Univ, Dept Biol Chem, BNLMS, Beijing 100871, Peoples R China 3.Peking Univ, Coll Chem, State Key Lab Mol Dynam & Stable Struct, Beijing 100871, Peoples R China 4.Oakland Univ, Dept Biol Sci, Rochester, MI 48309 USA 5.Peking Univ, Sch Basic Med Sci, Lab Med Immunol, Beijing 100871, Peoples R China 6.Shanghai Jiao Tong Univ, Coll Agr & Biotechnol, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Jingna,Wan, Wuzhou,Sun, Ronghua,et al. Reduction of Akt2 expression inhibits chemotaxis signal transduction in human breast cancer cells[J]. CELLULAR SIGNALLING,2008,20(6):1025-1034. |
| APA | Wang, Jingna.,Wan, Wuzhou.,Sun, Ronghua.,Liu, Ying.,Sun, Xiangjun.,...&Zhang, Ning.(2008).Reduction of Akt2 expression inhibits chemotaxis signal transduction in human breast cancer cells.CELLULAR SIGNALLING,20(6),1025-1034. |
| MLA | Wang, Jingna,et al."Reduction of Akt2 expression inhibits chemotaxis signal transduction in human breast cancer cells".CELLULAR SIGNALLING 20.6(2008):1025-1034. |
入库方式： OAI收割
来源：化学研究所
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