Título:
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Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer.
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Autor/a:
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Corominas-Faja, Bruna; Vellon, Luciano; Cuyàs, Elisabet; Buxó, Maria; Martin-Castillo, Begoña; Serra i Cucurull, Dolors; García Gómez, Jordi; Menendez, Javier A.; Lupu, Ruth
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Otros autores:
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Universitat de Barcelona |
Abstract:
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Fatty acid synthase (FASN) is a key lipogenic enzyme for de novo fatty acid biosynthesis and a druggable metabolic oncoprotein that is activated in most human cancers. We evaluated whether the HER2-driven lipogenic phenotype might represent a biomarker for sensitivity to pharmacological FASN blockade. A majority of clinically HER2-positive tumors were scored as FASN overexpressors in a series of almost 200 patients with invasive breast carcinoma. Re-classification of HER2-positive breast tumors based on FASN gene expression predicted a significantly inferior relapse-free and distant metastasis-free survival in HER2+/FASN+ patients. Notably, non-tumorigenic MCF10A breast epithelial cells engineered to overexpress HER2 upregulated FASN gene expression, and the FASN inhibitor C75 abolished HER2-induced anchorage-independent growth and survival. Furthermore, in the presence of high concentrations of C75, HER2-negative MCF-7 breast cancer cells overexpressing HER2 (MCF-7/HER2) had significantly higher levels of apoptosis than HER2-negative cells. Finally, C75 at non-cytotoxic concentrations significantly reduced the capacity of MCF-7/HER2 cells to form mammospheres, an in vitro indicator of cancer stem-like cells. Collectively, our findings strongly suggest that the HER2-FASN lipogenic axis delineates a group of breast cancer patients that might benefit from treatment with therapeutic regimens containing FASN inhibitors. |
Materia(s):
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-Àcids grassos -Càncer de mama -Fatty acids -Breast cancer |
Derechos:
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(c) Sercrisma International, 2016
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Tipo de documento:
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Artículo Artículo - Versión aceptada |
Editor:
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Sercrisma International
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Compartir:
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