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MEMO1, a new IRS1-interacting protein, induces epithelial–mesenchymal transition in mammary epithelial cells

Oncogene volume 32, pages 3130–3138 (2013)Cite this article

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Abstract

MEMO1 (mediator of ErbB2-driven cell motility 1) regulates HER2-dependent cell migration. Increased MEMO1 expression is associated with cancer aggressiveness. Here, we found that MEMO1 is also involved in breast carcinogenesis via regulating insulin-like growth factor-I receptor-dependent signaling events. We showed that MEMO1 binds to insulin receptor substrate 1, activates the downstream PI3K/Akt signaling pathway, leads to upregulation of Snail1 and thereby triggers the epithelial-mesenchymal transition (EMT) program. In addition, MEMO1 overexpression is accompanied by growth factor-independent proliferation, anchorage-independent growth in soft agar, and enhanced metastatic potential. Together, these findings suggest that MEMO1 acts as an oncogene and is a potential therapeutic target for cancer treatment.

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Acknowledgements

We thank all our colleagues in the Chen laboratory for insightful discussions and technical assistance. We thank Dr Douglas Yee at the University of Minnesota for sharing hIRS2 cDNA and Dr Cosima Baldari at the University of Siena (Italy) for sharing ShcA(p66) cDNA. This work was supported in part by an Era of Hope Research award to JC (W81XWH-09-1-0409). JC is also a recipient of an Era of Hope Scholar award from the Department of Defense (W81XWH-05-1-0470). This work was supported by MD Anderson’s Cancer Center Support Grant (CA016672).

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  1. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    A V Sorokin & J Chen

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Correspondence to J Chen.

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Sorokin, A., Chen, J. MEMO1, a new IRS1-interacting protein, induces epithelial–mesenchymal transition in mammary epithelial cells. Oncogene 32, 3130–3138 (2013). https://doi.org/10.1038/onc.2012.327

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