Please use this identifier to cite or link to this item:
https://hdl.handle.net/2445/108203
Title: | Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer. |
Author: | Corominas-Faja, Bruna Vellon, Luciano Cuyàs, Elisabet Buxó, Maria Martin Castillo, Begoña Serra i Cucurull, Dolors García Gómez, Jordi Menéndez, Javier A. Lupu, Ruth |
Keywords: | Àcids grassos Càncer de mama Fatty acids Breast cancer |
Issue Date: | 3-Apr-2017 |
Publisher: | Sercrisma International |
Abstract: | 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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.14670/HH-11-830 |
It is part of: | Histology and Histopathology, 2017, vol. 32, num. 7. p. 687-698 |
URI: | https://hdl.handle.net/2445/108203 |
Related resource: | https://doi.org/10.14670/HH-11-830 |
ISSN: | 0213-3911 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Fisiologia) Articles publicats en revistes (Química Inorgànica i Orgànica) |
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667434.pdf | 4.89 MB | Adobe PDF | View/Open |
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