Magi1, a new potential tumor suppressor gene in estrogen receptor positive breast cancer

Alday-Parejo, Begoña; Richard, François; Wörthmüller, Janine; Rau, Tilman; Galván, José A.; Desmedt, Christine; Santamaria-Martinez, Albert; Rüegg, Curzio

doi:10.3390/cancers12010223

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Journal article

Magi1, a new potential tumor suppressor gene in estrogen receptor positive breast cancer

Alday-Parejo, Begoña Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Richard, François Laboratory for Translational Breast Cancer Research, KU Leuven, 3001 Leuven, Belgium
Wörthmüller, Janine Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Rau, Tilman Institute of Pathology, University of Bern, 3008 Bern, Switzerland
Galván, José A. Institute of Pathology, University of Bern, 3008 Bern, Switzerland
Desmedt, Christine Laboratory for Translational Breast Cancer Research, KU Leuven, 3001 Leuven, Belgium
Santamaria-Martinez, Albert Tumor Ecology Laboratory, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Rüegg, Curzio Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, 1700 Fribourg, Switzerland

16.01.2020

Published in:

Cancers. - 2020, vol. 12, no. 1, p. 223

English Membrane-associated guanylate kinase (MAGUK) with inverted domain structure-1 (MAGI1) is an intracellular adaptor protein that stabilizes epithelial junctions consistent with a tumor suppressive function in several cancers of epithelial origin. Here we report, based on experimental results and human breast cancer (BC) patients’ gene expression data, that MAGI1 is highly expressed and acts as tumor suppressor in estrogen receptor (ER)+/HER2− but not in HER2+ or triple negative breast cancer (TNBC). Within the ER+/HER2− subset, high MAGI1 expression associates with ESR1 and luminal genes GATA3 and FOXA1 expression and better prognosis, while low MAGI1 levels correlates with higher histological grade, more aggressive phenotype and worse prognosis. Experimentally, MAGI1 downregulation in the ER+ human BC cells MCF7 impairs ER expression and signaling, promotes cell proliferation, and reduces apoptosis and epithelial differentiation. MAGI1 downregulation in the ER+ murine BC cell line 67NR accelerates primary tumor growth and enhances experimental lung metastasis formation. MAGI1 expression is upregulated by estrogen/ER, downregulated by prostaglandin E2/COX-2axis, and negatively correlates with inflammation in ER+/HER2− BC patients. Taken together, we show that MAGI1 is a new potential tumor suppressor in ER+/HER2− breast cancer with possible prognostic value for the identification of patients at high- risk of relapse within this subset.

Faculty

Faculté des sciences et de médecine

Department

Médecine 3ème année

Language