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N-cadherin regulates mammary tumor cell migration through Akt3 suppression

Oncogene volume 32, pages 422–430 (2013)Cite this article

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Abstract

N-cadherin is a cell–cell adhesion molecule that plays a role in breast cancer metastasis. Here, we show that in vivo expression of N-cadherin in the PyMT mouse model, which enhances mammary tumor metastasis, results in selective inhibition of Akt3 expression and phosphorylation. Similarly, exogenous expression of N-cadherin in PyMT or MCF-7 mammary tumor cells enhanced cell motility and caused a dramatic reduction in Akt3 expression and phosphorylation. Moreover, knockdown of Akt3 in PyMT tumor cells increased cell motility and disrupted mammary morphogenesis, but had no effect on cell proliferation. Conversely, overexpression of wild-type Akt3 in PyMT-N-cadherin cells inhibited cell motility promoted by N-cadherin. Taken altogether, these findings demonstrate that N-cadherin suppresses Akt3 to promote cell motility and highlight the intricate regulation of Akt isoforms by N-cadherin during metastasis.

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Acknowledgements

This study was supported by grants from National Cancer Institute (Grant 1R01 CA135061-01A1) the NIH and Breast Cancer Research Foundation (to RB Hazan). Su Chung was partly supported by the Training Program in Cellular and Molecular Biology and Genetics (T32 GM007491).

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Authors and Affiliations

  1. Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA

    S Chung, J Yao, K Suyama, S Bajaj, X Qian, O D Loudig, E A Eugenin & R B Hazan

  2. Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA

    G R Phillips

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  1. S Chung
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  2. J Yao
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  3. K Suyama
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  4. S Bajaj
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  7. E A Eugenin
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  8. G R Phillips
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  9. R B Hazan
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Correspondence to R B Hazan.

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Supplementary Information accompanies the paper on the Oncogene website

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Chung, S., Yao, J., Suyama, K. et al. N-cadherin regulates mammary tumor cell migration through Akt3 suppression. Oncogene 32, 422–430 (2013). https://doi.org/10.1038/onc.2012.65

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