p66ShcA promotes breast cancer plasticity by inducing an epithelial-to-mesenchymal transition
| Autor: | Lauren Podmore, Josie Ursini-Siegel, Nicole Beauchemin, Laura Forrest, Jacqueline R. Ha, Julie Livingstone, Ryuhjin Ahn, Jennifer F. Knight, Valerie Sabourin, Jesse Hudson, Michael Hallett, Rachel La Selva, Morag Park |
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| Rok vydání: | 2014 |
| Předmět: |
CA15-3
Epithelial-Mesenchymal Transition Src Homology 2 Domain-Containing Transforming Protein 1 Receptor ErbB-2 Breast Neoplasms Disease Mice SCID Biology Mice Breast cancer Cell Movement Cell Line Tumor medicine Biomarkers Tumor Animals Humans Epithelial–mesenchymal transition Receptor skin and connective tissue diseases Molecular Biology Mesenchymal stem cell Signal transducing adaptor protein Mammary Neoplasms Experimental Cell Biology Articles Proto-Oncogene Proteins c-met medicine.disease Gene Expression Regulation Neoplastic Shc Signaling Adaptor Proteins Immunology Cancer research Female Signal transduction Signal Transduction |
| Zdroj: | Molecular and cellular biology. 34(19) |
| ISSN: | 1098-5549 |
| Popis: | Breast cancers are stratified into distinct subtypes, which influence therapeutic responsiveness and patient outcome. Patients with luminal breast cancers are often associated with a better prognosis relative to that with other subtypes. However, subsets of patients with luminal disease remain at increased risk of cancer-related death. A critical process that increases the malignant potential of breast cancers is the epithelial-to-mesenchymal transition (EMT). The p66ShcA adaptor protein stimulates the formation of reactive oxygen species in response to stress stimuli. In this paper, we report a novel role for p66ShcA in inducing an EMT in HER2(+) luminal breast cancers. p66ShcA increases the migratory properties of breast cancer cells and enhances signaling downstream of the Met receptor tyrosine kinase in these tumors. Moreover, Met activation is required for a p66ShcA-induced EMT in luminal breast cancer cells. Finally, elevated p66ShcA levels are associated with the acquisition of an EMT in primary breast cancers spanning all molecular subtypes, including luminal tumors. This is of high clinical relevance, as the luminal and HER2 subtypes together comprise 80% of all newly diagnosed breast cancers. This study identifies p66ShcA as one of the first prognostic biomarkers for the identification of more aggressive tumors with mesenchymal properties, regardless of molecular subtype. |
| Databáze: | OpenAIRE |
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