title: MEMO1, a new IRS1-interacting protein, induces epithelial-mesenchymal transition in mammary epithelial cells.
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.
authors: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: A V
authors: AV
authors: Sorokin
authors: J
authors: J
authors: Chen
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D042361:Mammary Glands, Human / Q000378:metabolism*; D009362:Neoplasm Metastasis; D019159:Nonheme Iron Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D066246:ErbB Receptors; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019159:Nonheme Iron Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C526292:IRS1 protein, human; C527585:MEMO1 protein, human; C000604407:SNAI1 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human