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


IntroductionN-myc downstream-regulated gene 2 (NDRG2), a novel tumour suppressor and cell stress-related gene, is involved in many cell metabolism processes, such as hormone, ion and fluid metabolism. We investigated whether NDRG2 is involved in any glucose-dependent energy metabolism, and 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 in transcription and translation level and the interaction between NDRG2 and GLUT1 were examined.

Results:
Data from clinical breast carcinoma specimens revealed that patients with high NDRG2 expression had better disease-free survival and overall survival than those with low NDRG2 expression, and 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 co-localised with GLUT1 protein at cell cytoplasm areas.

Conclusions:
Our study supports the notion that NDRG2 plays an important role in tumour glucose metabolism, in which GLUT1 is a likely candidate to contribute to suppress glucose uptake 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.

Author: Ji MaWenchao LiuHang GuoShaoqing LiWei CaoXilin DuShixiong LeiWugang HouLize XiongLibo YaoNanlin LiYan Li
Credits/Source: Breast Cancer Research 2014, 16:R27

Published on: 2014-03-18

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