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


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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 epithelialmesenchymal 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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