N-myc downstream-regulated gene 2 expression is associated with glucose transport and correlated with prognosis in breast carcinoma

INTRODUCTION: N-myc downstream-regulated gene 2 (NDRG2), a novel tumour suppressor and cell stress-related gene, is involved in many cell metabolic processes, such as hormone, ion and fluid metabolism. We investigated whether NDRG2 is involved in any glucose-dependent energy metabolism, as well as the nature of its correlation with breast carcinoma. METHODS: The correlations between NDRG2 expression and glucose transporter 1 (GLUT1) expression in clinical breast carcinoma tissues were analysed. The effects of NDRG2 on glucose uptake were assessed in breast cancer cells and xenograft tumours. The consequences of NDRG2-induced regulation of GLUT1 at the transcription and translation levels and the interaction between NDRG2 and GLUT1 were examined. RESULTS: Data derived from clinical breast carcinoma specimens revealed that (1) patients with high NDRG2 expression had better disease-free survival and overall survival than those with low NDRG2 expression and (2) NDRG2 expression was negatively correlated with GLUT1 expression in these breast carcinoma tissues. NDRG2 inhibited glucose uptake by promoting GLUT1 protein degradation without affecting GLUT1 transcription in both breast cancer cells and xenograft tumours. In addition, NDRG2 protein interacted and partly colocalised with GLUT1 protein in cell cytoplasm areas. CONCLUSIONS: The results of our study support the notion that NDRG2 plays an important role in tumour glucose metabolism, in which GLUT1 is a likely candidate contributor to glucose uptake suppression and tumour growth. Targeting the actions of NDRG2 in cell glucose-dependent energy delivery may provide an attractive strategy for therapeutic intervention in human breast carcinoma.