Decreasing the survival ability of brain metastatic breast cancer cell by targeting glucose transporter 3

Abstract

Breast cancer brain metastases (BBMs) are found in 15–20 % of breast cancer patients. And it results in a high mortality once the brain metastases are diagnosed. Therefore, making it more comprehensive about the mechanisms of BBMs is emergently necessary. Several studies have demonstrated that tumor microenvironment has potent roles in the tumor progression and metastasis. Besides, according to the former studies, cells in different organs using glucose might be various; as well as the dominant glucose transporters used are distinct. Here, we analyzed the brain metastatic breast cancer (BR) cells collected from intracardiac injection of nude mice and found the utilization of glucose transporters in the BR cells were different from the parental breast cancer cells; the elevated expressions of glucose transporter 3 were observed. In addition, the higher anaerobic glycolysis ability was found in BR cells. And after GLUT3 knockdown, the glucose reprogramming in BR cells was significantly decreased as well as the cancer malignant behaviors both in vitro and in vivo. Besides manipulating GLUT3 expressions, we also provide a potential mechanism that CREB could be a potent regulator of GLUT3 in BR cells by chromatin immunoprecipitation (ChIP) and knockdown assay. After decreasing the expressions of CREB in BR cells, the expressions of GLUT3 were also significantly reduced. In sum, our results reveal that GLUT3 plays an important role in provoking breast cancer cells surviving in brain by mediating glucose utilizations. And these results could provide a potential therapeutic way to target BBMs.Support or Funding Information1. Ministry of Science and Technology, R.O.C 2. Molecular Medicine Taiwan International Graduate Program, Academia Sinica