Down-regulation of FBP1 by ZEB1-mediated repression confers to growth and invasion in lung cancer cells.

Lung cancer is the most common type of malignant tumor, but the molecular mechanisms for lung cancer progression remains to be elusive. Here, we demonstrated that FBP1 (Fructose-1, 6-bisphosphatase) was frequently down-regulated in lung cancer tissues and cells, and FBP1 down-regulation was associated with poor prognosis in lung cancer patients. Restored FBP1 expression inhibited glucose uptake and lactate production, but induced oxygen consumption. Restored FBP1 expression also inhibited lung cancer cells proliferation and invasion under hypoxia in vitro, and inhibited lung cancer growth in vivo. Moreover, we confirmed DNA methylation in the promoter contributed to the decrease of FBP1 expression in lung cancer cells. We identified Zinc finger E-box-binding homeobox 1 (ZEB1) bond to FBP1 promoter to enhance DNA methylation in lung cancer cells. Our findings indicate that the down-regulation of FBP1 is a critical oncogenic event in lung cancer progression.