FBP1 modulates cell metabolism of breast cancer cells by inhibiting the expression of HIF-1α

Abstract

This study aimed to investigate the function of fructose-1, 6-bisphosphatase 1 (FBP1) in regulating cell growth and metabolism through hypoxia-inducible factor 1α (HIF-1α)-dependent hypoxic response in breast cancer cells. Two human breast carcinoma cell lines, including luminal-like cell line MCF-7 and basal-like cell line MDA-MB-468, were cultured under hypoxia condition, then the expressions of FBP1 and HIF-1α were detected by western blotting. In addition, up-regulated FPB1 in MDA-MB-468 cells were induced by lentivirus. Next, cell growth, migration and glucose metabolism were evaluated by MTT assay, Transwell and commercial kits, as well as the expressions of HIF-1α target genes, including pyruvate dehydrogenase kinase 1 (PDK1), lactate dehydrogenase A (LDHA), glucose transporter 1 (GLUT1) and vascular endothelial growth factor (VEGF) were detected by RT-qPCR. Furthermore, chromatin immunoprecipitation was used to estimate whether the hypoxia response elements (HREs) of PDK1, LDHA, GLUT1 and VEGF promoters were incorporated with FBP1. FBP1 was downregulated in MDA-MB-468 cells compared with MCF-7 cells. Overexpression of FBP1 in MDA-MB-468 cells reduced cell growth (p < 0.05) and migration (p < 0.05) as well as glycose consumption (p < 0.05) and lactate production (p < 0.05). In addition, overexpressed FBP1 inhibited HIF-1α protein expression and the mRNA levels of PDK1, LDHA, GLUT1 and VEGF (p < 0.05) under hypoxia condition. Also, FBP1 was revealed to have a concrete connection with PDK1. This study reveal that overexpressed FBP1 may repress tumor growth, migration and glycolysis via targeting HIF-1α in BLBC.

Keywords: 6-bisphosphatase 1 glucose metabolism.; basal-like breast carcinoma; fructose-1; hypoxia-inducible factor-1α.