Role of Fatty Acid Binding Protein 5 (FABP5) in Breast Cancer Progression and Metastasis.

摘要

Fatty acid binding protein 5 (FABP5) is a small, 14-15 kDa, molecular weight intracellular fatty acid shuttle. FABP5 functions to shuttle long chain fatty acids from the extracellular environment to the nucleus. These fatty acids are then used as ligands for nuclear receptors and activate transcription. FABP5 has been shown to coordinate metabolic and inflammatory responses in adipocytes and may play a role in the development of obesity- mediated breast cancer. Both FABP5 and S100A7 proteins are over-expressed in the inflammatory skin disease, psoriasis. Additionally, there is evidence that these two proteins associate with one another. Previously reported by our lab, S100A7 enhances tumor progression in orthotopic breast cancer mouse models. Taking together the evidence of S100A7 in breast cancer progression and the support that FABP5 is involved in breast cancer development and progression. We have shown overexpression of FABP5 in mammary glands of mice overexpressing mS100a7a15, the mouse homolog of human S100A7. FABP5 was also shown to be expressed higher in S100A7 overexpressing triple negative breast cancer cells compared to vector control. Additionally, FABP5 has higher expression in a highly metastatic breast cancer cell line compared to a low metastatic breast cancer cell line. We determined FABP5 knockout in the host significantly decreases tumor volume in an orthotopic model of breast cancer. We showed that shRNA mediated FABP5 knockdown in triple negative breast cancer cells results in less migration compared to scrambled shRNA. Additional cell lines are being evaluated and used to validate these results. FABP5 expression was examined in a tumor microarray and found that FABP5 expression is correlated with higher tumor grade and triple negative breast cancer. Additionally, high FABP5 protein expression is associated with shorter disease free recurrence.