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

Bruna Corominas-Faja, Luciano Vellon, Elisabet Cuyàs, Maria Buxó, Begoña Martin-Castillo, Dolors Serra, Jordi García, Javier A. Menendez, Ruth Lupu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Summary. 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. Reclassification 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.

Original languageEnglish (US)
Pages (from-to)687-698
Number of pages12
JournalHistology and Histopathology
Volume32
Issue number7
DOIs
StatePublished - Jul 1 2017

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Fatty Acid Synthases
Oncogenes
Breast Neoplasms
Therapeutics
Gene Expression
Survival
Neoplastic Stem Cells
Oncogene Proteins
Neoplasms
Breast
Fatty Acids
Biomarkers
Epithelial Cells
Pharmacology
Apoptosis
Neoplasm Metastasis
Phenotype
Recurrence

Keywords

  • Breast cancer
  • C75
  • Fatty acid syntase
  • HER2

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer. / Corominas-Faja, Bruna; Vellon, Luciano; Cuyàs, Elisabet; Buxó, Maria; Martin-Castillo, Begoña; Serra, Dolors; García, Jordi; Menendez, Javier A.; Lupu, Ruth.

In: Histology and Histopathology, Vol. 32, No. 7, 01.07.2017, p. 687-698.

Research output: Contribution to journalArticle

Corominas-Faja, B, Vellon, L, Cuyàs, E, Buxó, M, Martin-Castillo, B, Serra, D, García, J, Menendez, JA & Lupu, R 2017, 'Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer', Histology and Histopathology, vol. 32, no. 7, pp. 687-698. https://doi.org/10.14670/HH-11-830
Corominas-Faja B, Vellon L, Cuyàs E, Buxó M, Martin-Castillo B, Serra D et al. Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer. Histology and Histopathology. 2017 Jul 1;32(7):687-698. https://doi.org/10.14670/HH-11-830
Corominas-Faja, Bruna ; Vellon, Luciano ; Cuyàs, Elisabet ; Buxó, Maria ; Martin-Castillo, Begoña ; Serra, Dolors ; García, Jordi ; Menendez, Javier A. ; Lupu, Ruth. / Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer. In: Histology and Histopathology. 2017 ; Vol. 32, No. 7. pp. 687-698.
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