Matriptase regulates c-Met mediated proliferation and invasion in inflammatory breast cancer
| Autor: | Lauren M. Tanabe, Michael J. Duhaime, Éloïc Colombo, Karin List, Michael D. Johnson, Chen-Yong Lin, Thomas E. Hyland, Julie L. Boerner, Julie E. Lang, Richard Leduc, Gina L. Zoratti, Eric Marsault |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Cell Culture Techniques matriptase Targeted therapy chemistry.chemical_compound 0302 clinical medicine 2.1 Biological and endogenous factors Aetiology RNA Small Interfering skin and connective tissue diseases Cancer Tumor biology Hepatocyte Growth Factor Serine Endopeptidases Proto-Oncogene Proteins c-met Immunohistochemistry 3. Good health type II transmembrane serine proteases Oncology 5.1 Pharmaceuticals 030220 oncology & carcinogenesis RNA Interference Female Inflammatory Breast Neoplasms Signal transduction Development of treatments and therapeutic interventions Research Paper Signal Transduction C-Met Oncology and Carcinogenesis Small Interfering Inflammatory breast cancer Cell Line 03 medical and health sciences Rare Diseases Cell Line Tumor Breast Cancer medicine Gene silencing Humans Matriptase Neoplasm Invasiveness Protein Precursors Cell Proliferation business.industry Cell Membrane medicine.disease 030104 developmental biology chemistry Cancer cell Immunology Proteolysis Cancer research biology.protein RNA business inflammatory breast cancer |
| Zdroj: | Oncotarget, vol 7, iss 36 Oncotarget |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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