title: Memo interacts with c-Src to control Estrogen Receptor alpha sub-cellular localization.
abstract: Understanding the complex interaction between growth factor and steroid hormone signaling pathways in breast cancer is key to identifying suitable therapeutic strategies to avoid progression and therapy resistance. The interaction between these two pathways is of paramount importance for the development of endocrine resistance. Nevertheless, the molecular mechanisms behind their crosstalk are still largely obscure. We previously reported that Memo is a small redox-active protein that controls heregulin-mediated migration of breast cancer cells. Here we report that Memo sits at the intersection between heregulin and estrogen signaling, and that Memo controls Estrogen Receptor alpha (ERα) sub-cellular localization, phosphorylation, and function downstream of heregulin and estrogen in breast cancer cells. Memo facilitates ERα and c-Src interaction, ERα Y537 phosphorylation, and has the ability to control ERα extra-nuclear localization. Thus, we identify Memo as an important key mediator between the heregulin and estrogen signaling pathways, which affects both breast cancer cell migration and proliferation.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Frei
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse, Basel, Switzerland.
authors.forename: Gwen
authors.initials: G
authors.lastname: MacDonald
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lund
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.|Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Hynes
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Ivan
authors.initials: I
authors.lastname: Nalvarte
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000081247:CSK Tyrosine-Protein Kinase; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D061986:MCF-7 Cells; D008856:Microscopy, Fluorescence; D020890:Neuregulin-1 / Q000378:metabolism; D019159:Nonheme Iron Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D047908:Intracellular Signaling Peptides and Proteins; C527585:MEMO1 protein, human; C094131:NRG1 protein, human; D020890:Neuregulin-1; D019159:Nonheme Iron Proteins; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human
keywords: ER alpha; Memo1; c-Src; estrogen; heregulin