Regulation of miRNA expression by Src and contact normalization: effects on nonanchored cell growth and migration

被引:40
|
作者
Li, X. [1 ,2 ]
Shen, Y. [1 ]
Ichikawa, H. [3 ]
Antes, T. [4 ]
Goldberg, G. S. [1 ]
机构
[1] Univ Med & Dent New Jersey, Dept Mol Biol, Stratford, NJ 08084 USA
[2] Univ Med & Dent New Jersey, Grad Sch Biomed Sci, Stratford, NJ 08084 USA
[3] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 104, Japan
[4] Syst Biosci SBI, Mountain View, CA USA
基金
美国国家卫生研究院;
关键词
Src; contact normalization; cell communication; anchorage independence; migration; cancer; GAP JUNCTIONAL COMMUNICATION; BREAST-CANCER; MICRORNA EXPRESSION; TRANSFORMED-CELLS; HEPATOCELLULAR-CARCINOMA; NONTRANSFORMED CELLS; IN-VIVO; V-CRK; INHIBITION; INVASION;
D O I
10.1038/onc.2009.278
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transformation by the Src tyrosine kinase (Src) promotes nonanchored cell growth and migration. However, non-transformed cells can force Src-transformed cells to assume a normal morphology and phenotype by a process called 'contact normalization'. It has become clear that microRNA (miRNA) can affect tumorigenesis by targeting gene products that direct cell growth and migration. However, the roles of miRNA in Src transformation or contact normalization have not yet been reported. We examined the expression of 95 miRNAs and found 9 of them significantly affected by Src. In this study, we report that miR-218 and miR-224 were most significantly induced by Src, but not affected by contact normalization. In contrast, miR-126 was most significantly suppressed by Src and was induced by contact normalization in transformed cells. Mir-126 targets Crk, a component of the focal adhesion network that participates in events required for tumor cell migration. Accordingly, we show that miR-126 expression correlates inversely with Crk levels, motility and the invasive potential of human mammary carcinoma cells. Moreover, we show that miR-224 expression promotes nonanchored growth of nontransformed cells. These data reveal novel insights into how Src regulates miRNA expression to promote hallmarks of tumor cell growth and invasion, and how nontransformed cells can affect miRNA expression in adjacent tumor cells to inhibit this process. Oncogene (2009) 28, 4272-4283; doi: 10.1038/onc.2009.278; published online 21 September 2009
引用
收藏
页码:4272 / 4283
页数:12
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