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  • p66ShcA promotes breast cancer plasticity by inducing an epithelial-to-mesenchymal transition.

p66ShcA promotes breast cancer plasticity by inducing an epithelial-to-mesenchymal transition.

Molecular and cellular biology (2014-07-30)
Jesse Hudson, Jacqueline R Ha, Valerie Sabourin, Ryuhjin Ahn, Rachel La Selva, Julie Livingstone, Lauren Podmore, Jennifer Knight, Laura Forrest, Nicole Beauchemin, Michael Hallett, Morag Park, Josie Ursini-Siegel
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Phosphotyrosine MET / Hepatocyte Growth Factor Receptor ELISA Kit
Sigma-Aldrich
Human MET / Hepatocyte Growth Factor Receptor ELISA Kit
Sigma-Aldrich
Mouse HGF ELISA Kit, for serum, plasma and cell culture supernatant
Sigma-Aldrich
Mouse HGF ELISA Kit, for cell and tissue lysates
Sigma-Aldrich
Human HGF ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Human HGF ELISA Kit, for cell and tissue lysates