title: The adaptor protein AMOT promotes the proliferation of mammary epithelial cells via the prolonged activation of the extracellular signal-regulated kinases.
abstract: The asymmetric organization of epithelial cells is a basic counter to cellular proliferation. However, the mechanisms whereby pro-growth pathways are modulated by intracellular factors that control cell shape are not well understood. This study demonstrates that the adaptor protein Amot, in addition to its established role in regulating cellular asymmetry, also promotes extracellular signal-regulated kinase 1 and 2 (ERK1/2)-dependent proliferation of mammary cells. Specifically, expression of Amot80, but not a mutant lacking its polarity protein interaction domain, enhances ERK1/2-dependent proliferation of MCF7 cells. Further, expression of Amot80 induces nontransformed MCF10A cells to overgrow as disorganized cellular aggregates in Matrigel. Conversely, Amot expression is required for proliferation of breast cancer cells in specific microenvironmental contexts that require ERK1/2 signaling. Thus, Amot is proposed to coordinate the dysregulation of cell polarity with the induction of neoplastic growth in mammary cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Indiana School of Medicine, Indianapolis, Indiana 46202-5122, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: Ranahan
authors.forename: Zhang
authors.initials: Z
authors.lastname: Han
authors.forename: Whitney
authors.initials: W
authors.lastname: Smith-Kinnaman
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Nabinger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Heller
authors.forename: Britney-Shea
authors.initials: BS
authors.lastname: Herbert
authors.forename: Rebecca
authors.initials: R
authors.lastname: Chan
authors.forename: Clark D
authors.initials: CD
authors.lastname: Wells
mesh_terms: D000091082:Angiomotins; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen; D004338:Drug Combinations; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009154:Mutation; D011509:Proteoglycans; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D059016:Tumor Microenvironment
chemical_list: C423985:AMOT protein, human; D000091082:Angiomotins; D004338:Drug Combinations; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D008164:Luminescent Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3