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2017-04-03

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/108203

Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer.

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Recurs relacionat

https://doi.org/10.14670/HH-11-830

Resum

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.

Matèries

Àcids grassos, Càncer de mama

Matèries (anglès)

Fatty acids, Breast cancer

Citació

Col·leccions

Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Química Inorgànica i Orgànica)

Citació

COROMINAS-FAJA, Bruna, et al. Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer. Histology and Histopathology. 2017. Vol. 32, num. 7. ISSN 0213-3911. [consulted: 16 of August of 2026]. Available at: https://hdl.handle.net/2445/108203

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