Oncotarget

Research Papers:

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

Anna Frei, Gwen MacDonald, Ingrid Lund, Jan-Åke Gustafsson, Nancy E. Hynes and Ivan Nalvarte _

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Oncotarget. 2016; 7:56170-56182. https://doi.org/10.18632/oncotarget.10856

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Abstract

Anna Frei1,4, Gwen MacDonald1, Ingrid Lund2, Jan-Åke Gustafsson2,3, Nancy E. Hynes1,4 and Ivan Nalvarte2

1 Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse, Basel, Switzerland

2 Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden

3 Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX, USA

4 University of Basel, Basel, Switzerland

Correspondence to:

Ivan Nalvarte, email:

Keywords: Memo1, heregulin, ER alpha, estrogen, c-Src

Received: June 30, 2016 Accepted: July 14, 2016 Published: July 26, 2016

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.


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PII: 10856