Reduction of Akt2 expression inhibits chemotaxis signal transduction in   human breast cancer cells

doi:10.1016/j.cellsig.2007.12.023

CORC > 北京大学 > 化学与分子工程学院

	Reduction of Akt2 expression inhibits chemotaxis signal transduction in human breast cancer cells
	Wang, Jingna ; Wan, Wuzhou ; Sun, Ronghua ; Liu, Ying ; Sun, Xiangjun ; Ma, Dalong ; Zhang, Ning
刊名	cellular signalling
	2008
关键词	Akt2 chemotaxis metastasis PKC xi EGF ACTIN POLYMERIZATION ROLES PROTEIN MOTILITY INVASION CDC42 METASTASIS RECEPTORS MIGRATION POLARITY
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.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000256238600004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Cell Biology; SCI(E); PubMed; 16; ARTICLE; 6; 1025-1034; 20
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/199195]
专题	化学与分子工程学院
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.
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.
MLA	Wang, Jingna,et al."Reduction of Akt2 expression inhibits chemotaxis signal transduction in human breast cancer cells".cellular signalling (2008).