FABP7 is a key metabolic regulator in HER2+ breast cancer brain metastasis.
Alex CorderoDeepak KanojiaJason MiskaWojciech K PanekAnnie XiaoYu HanNicolas BonamiciWeidong ZhouTing XiaoMeijing WuAtique U AhmedMaciej S LesniakPublished in: Oncogene (2019)
Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer patients is associated with increased incidence of breast cancer brain metastases (BCBM), but the mechanisms underlying this phenomenon remain unclear. Here, to identify brain-predominant genes critical for the establishment of BCBM, we conducted an in silico screening analysis and identified that increased levels of fatty acid-binding protein 7 (FABP7) correlate with a lower survival and higher incidence of brain metastases in breast cancer patients. We validated these findings using HER2+ BCBM cells compared with parental breast cancer cells. Importantly, through knockdown and overexpression assays, we characterized the role of FABP7 in the BCBM process in vitro and in vivo. Our results uncover a key role of FABP7 in metabolic reprogramming of HER2 + breast cancer cells, supporting a glycolytic phenotype and storage of lipid droplets that enable their adaptation and survival in the brain microenvironment. In addition, FABP7 is shown to be required for upregulation of key metastatic genes and pathways, such as integrins-Src and VEGFA, and for the growth of HER2+ breast cancer cells in the brain microenvironment in vivo. Together, our results support FABP7 as a potential target for the treatment of HER2+ BCBM.
Keyphrases
- binding protein
- breast cancer cells
- brain metastases
- small cell lung cancer
- epidermal growth factor receptor
- resting state
- white matter
- fatty acid
- tyrosine kinase
- stem cells
- cell proliferation
- transcription factor
- functional connectivity
- risk factors
- squamous cell carcinoma
- endothelial cells
- cerebral ischemia
- genome wide
- induced apoptosis
- molecular docking
- advanced non small cell lung cancer
- poor prognosis
- multiple sclerosis
- cell death
- brain injury
- oxidative stress
- free survival
- smoking cessation
- data analysis
- pi k akt
- induced pluripotent stem cells