Fatty acid synthase phosphorylation: a novel therapeutic target in HER2-overexpressing breast cancer cells
Open Access
- 16 November 2010
- journal article
- Published by Springer Science and Business Media LLC in Breast Cancer Research
- Vol. 12 (6), R96
- https://doi.org/10.1186/bcr2777
Abstract
The human epidermal growth factor receptor 2 (HER2) is a validated therapeutic target in breast cancer. Heterodimerization of HER2 with other HER family members results in enhanced tyrosine phosphorylation and activation of signal transduction pathways. HER2 overexpression increases the translation of fatty acid synthase (FASN), and FASN overexpression markedly increases HER2 signaling, which results in enhanced cell growth. However, the molecular mechanism and regulation of HER2 and FASN interaction are not well defined. Lapatinib is a small-molecule tyrosine kinase inhibitor that blocks phosphorylation of the epidermal growth factor receptor and HER2 in breast cancer cells, resulting in apoptosis. We hypothesized that FASN is directly phosphorylated by HER2, resulting in enhanced signaling and tumor progression in breast cancer cells.Keywords
This publication has 48 references indexed in Scilit:
- Lapatinib Combined With Letrozole Versus Letrozole and Placebo As First-Line Therapy for Postmenopausal Hormone Receptor–Positive Metastatic Breast CancerJournal of Clinical Oncology, 2009
- p63 Promotes Cell Survival through Fatty Acid SynthasePLOS ONE, 2009
- Peroxisome proliferator-activated receptor-γ protects ERBB2-positive breast cancer cells from palmitate toxicityBreast Cancer Research, 2009
- Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicityOncogene, 2008
- HER2 Oncogenic Function Escapes EGFR Tyrosine Kinase Inhibitors via Activation of Alternative HER Receptors in Breast Cancer CellsPLOS ONE, 2008
- Survivin expression in normal human bronchial epithelial cells: an early and critical step in tumorigenesis induced by tobacco exposureCarcinogenesis: Integrative Cancer Research, 2008
- Implication of AMP-Activated Protein Kinase and Akt-Regulated Survivin in Lung Cancer Chemopreventive Activities of DeguelinCancer Research, 2007
- Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor tyrosine kinase inhibitor protects cardiac cellsProceedings of the National Academy of Sciences of the United States of America, 2007
- ErbB3-Dependent Motility and Intravasation in Breast Cancer MetastasisCancer Research, 2006
- Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/ neu OncogeneScience, 1987