Oncotarget

Research Papers:

Matriptase regulates c-Met mediated proliferation and invasion in inflammatory breast cancer

Gina L. Zoratti _, Lauren M. Tanabe, Thomas E. Hyland, Michael J. Duhaime, Éloïc Colombo, Richard Leduc, Eric Marsault, Michael D. Johnson, Chen-Yong Lin, Julie Boerner, Julie E. Lang, Karin List

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Abstract

Gina L. Zoratti1,2, Lauren M. Tanabe2, Thomas E. Hyland2, Michael J. Duhaime2, Éloïc Colombo3, Richard Leduc3, Eric Marsault3, Michael D. Johnson4, Chen-Yong Lin4, Julie Boerner1, Julie E. Lang5, Karin List1,2

1Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA

2Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA

3Department of Pharmacology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H5N4 Canada

4Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington DC 20057, USA

5Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA

Correspondence to:

Karin List, email: klist@med.wayne.edu

Keywords: inflammatory breast cancer, matriptase, type II transmembrane serine proteases

Received: June 03, 2016     Accepted: July 29, 2016     Published: August 12, 2016

ABSTRACT

The poor prognosis for patients with inflammatory breast cancer (IBC) compared to patients with other types of breast cancers emphasizes the need to better understand the molecular underpinnings of this disease with the goal of developing effective targeted therapeutics. Dysregulation of matriptase expression, an epithelial-specific member of the type II transmembrane serine protease family, has been demonstrated in many different cancer types. To date, no studies have assessed the expression and potential pro-oncogenic role of matriptase in IBC. We examined the functional relationship between matriptase and the HGF/c-MET signaling pathway in the IBC cell lines SUM149 and SUM190, and in IBC patient samples. Matriptase and c-Met proteins are localized on the surface membrane of IBC cells and their expression is strongly correlated in infiltrating cancer cells and in the cancer cells of lymphatic emboli in patient samples. Abrogation of matriptase expression by silencing with RNAi or inhibition of matriptase proteolytic activity with a synthetic inhibitor impairs the conversion of inactive pro-HGF to active HGF and subsequent c-Met-mediated signaling, leading to efficient impairment of proliferation and invasion of IBC cells. These data show the potential of matriptase inhibitors as a novel targeted therapy for IBC, and lay the groundwork for the development and testing of such drugs.

Author Information

Gina L. Zoratti
Primary Contact  _

Lauren M. Tanabe

Thomas E. Hyland

Michael J. Duhaime

Éloïc Colombo

Richard Leduc

Eric Marsault

Michael D. Johnson

Chen-Yong Lin

Julie Boerner

Julie E. Lang

Karin List


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