The online version of this article (doi:10.1186/bcr3628) contains supplementary material, which is available to authorized users.
Ji Ma, Wenchao Liu, Hang Guo contributed equally to this work.
The authors declare that they have no competing interests.
All authors conceived of the study and participated in its design. JM, WCL and HG performed most of the experiments. SLi performed xenograft experiments. WC participated in all statistical analyses. XD and SLei provided formalin-fixed, paraffin-embedded, archived patient materials and conducted pathologic reviews and clinical data evaluations. WH performed immunostaining and quantitative analyses. NL and YL interpreted the data and drafted the manuscript. JM, WCL, HG, SLi, WC, XD, SLei, WH, LX and LY revised the manuscript critically. All authors read and approved the final manuscript.
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.
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.
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.
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.
Additional file 1: Table S1: The sequences of small interfering RNA or primers. (DOC 32 KB)13058_2013_3387_MOESM1_ESM.doc
Additional file 2: Figure S1: Negative control with human breast cancer tissues probed with isotype control IgG. Figure S2. NDRG2 is negatively correlated with GLUT1 in breast carcinoma. Figure S3. NDRG2 expression inversely correlated with GLUT1 expression in paired tumour and adjacent normal tissues of breast cancer patients. Figure S4. NDRG2 downregulates GLUT1 by promoting its ubiquitination. Figure S5. The interaction of exogenous NDRG2 and exogenous GLUT1. Figure S6. NDRG2 decreases the GLUT1 protein levels in SK-BR-3-based xenograft tumours. Figure S7. NDRG2 decreases the glucose uptake and GLUT1 protein levels in MDA-MB-231-based subcutaneously xenograft tumours. (DOC 2 MB)13058_2013_3387_MOESM2_ESM.doc
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- N-myc downstream-regulated gene 2 expression is associated with glucose transport and correlated with prognosis in breast carcinoma
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