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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Breast Neoplasms / metabolism
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Cell Line, Tumor
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Cell Proliferation
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Cell Transformation, Neoplastic
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Enzyme Activation
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Epithelial-Mesenchymal Transition / physiology*
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ErbB Receptors / metabolism
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Female
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Humans
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Insulin Receptor Substrate Proteins / metabolism*
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Intracellular Signaling Peptides and Proteins
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Mammary Glands, Human / metabolism*
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Neoplasm Metastasis
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Nonheme Iron Proteins / metabolism*
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Phosphatidylinositol 3-Kinases / metabolism
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Proto-Oncogene Proteins c-akt / metabolism
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Receptor, ErbB-2 / metabolism
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Receptor, IGF Type 1 / metabolism*
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Signal Transduction
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Snail Family Transcription Factors
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Transcription Factors / metabolism
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Up-Regulation
Substances
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IRS1 protein, human
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Insulin Receptor Substrate Proteins
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Intracellular Signaling Peptides and Proteins
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MEMO1 protein, human
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Nonheme Iron Proteins
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SNAI1 protein, human
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Snail Family Transcription Factors
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Transcription Factors
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EGFR protein, human
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ERBB2 protein, human
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ErbB Receptors
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Receptor, ErbB-2
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Receptor, IGF Type 1
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Proto-Oncogene Proteins c-akt