Memo interacts with c-Src to control Estrogen Receptor alpha sub-cellular localization

Oncotarget. 2016 Aug 30;7(35):56170-56182. doi: 10.18632/oncotarget.10856.

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.

Keywords: ER alpha; Memo1; c-Src; estrogen; heregulin.

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • CSK Tyrosine-Protein Kinase
  • Cell Movement
  • Cell Nucleus / metabolism
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Estrogen Receptor alpha / metabolism*
  • Estrogens / metabolism*
  • Female
  • Gene Knockdown Techniques
  • Humans
  • MCF-7 Cells
  • Microscopy, Fluorescence
  • Neuregulin-1 / metabolism
  • Nonheme Iron Proteins / genetics
  • Nonheme Iron Proteins / metabolism*
  • Phosphorylation
  • Signal Transduction
  • src-Family Kinases / metabolism*

Substances

  • Antineoplastic Agents, Hormonal
  • Estrogen Receptor alpha
  • Estrogens
  • MEMO1 protein, human
  • NRG1 protein, human
  • Neuregulin-1
  • Nonheme Iron Proteins
  • estrogen receptor alpha, human
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human