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

Oncogene volume 28, pages 4272–4283 (2009)Cite this article

Abstract

Transformation by the Src tyrosine kinase (Src) promotes nonanchored cell growth and migration. However, nontransformed 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.

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Acknowledgements

We thank Xiaofeng Ye and Reuben Lotan (MD Anderson Cancer Center) for helpful suggestions and for the gifts of cells, and Min Han (UMDNJ) for technical assistance. This study was supported by a grant from the United States National Institutes of Health (CA88805), the Research Foundation of UMDNJ, and the Marks and Holzman families to GSG, and by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan to HI.

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Authors and Affiliations

  1. UMDNJ-Graduate School of Biomedical Sciences, 2 Medical Center Drive, University of Medicine and Dentistry of New Jersey, Stratford, NJ, USA

    X Li

  2. Department of Molecular Biology, 2 Medical Center Drive,

    X Li, Y Shen & G S Goldberg

  3. University of Medicine and Dentistry of New Jersey, Stratford, NJ, USA

    X Li, Y Shen & G S Goldberg

  4. Genetics Division, National Cancer Center Research Institute, Tokyo, Japan

    H Ichikawa

  5. System Biosciences (SBI), Mountain View, CA, USA

    T Antes

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Correspondence to G S Goldberg.

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Li, X., Shen, Y., Ichikawa, H. et al. Regulation of miRNA expression by Src and contact normalization: effects on nonanchored cell growth and migration. Oncogene 28, 4272–4283 (2009). https://doi.org/10.1038/onc.2009.278

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