Details

Autor(en) / Beteiligte

• Zhang, Hong-Sheng
• Du, Guang-Yuan
• Zhang, Zhong-Guo
• Zhou, Zhen
• Sun, Hong-Liang
• Yu, Xiao-Ying
• Shi, Yu-Ting
• Xiong, Dan-Ning
• Li, Hu
• Huang, Ying-Hui

Titel

NRF2 facilitates breast cancer cell growth via HIF1ɑ-mediated metabolic reprogramming

Ist Teil von

• The international journal of biochemistry & cell biology, 2018-02, Vol.95, p.85-92

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •NRF2 and HIF1α up-regulated in breast cancer cells.•Knockdown of NRF2 inhibited glycolytic enzymes expression.•AKT activation and AMPK inhibition were required for NRF2-mediated up-regulation of glycolytic enzymes. High aerobic glycolysis not only provides energy to breast cancer cells, but also supports their anabolic growth. The redox sensitive transcription factor NRF2 is over-expressed in multiple cancers, including breast cancer. It is unclear whether NRF2 could promote breast cancer cell growth through enhancing glycolysis. In this study, we found that NRF2 and HIF1α mRNA and protein levels were significantly increased in MCF-7 and MDA-MB-231 breast cancer cells as compared to MCF-10A benign breast epithelial cells. Down-regulation of NRF2 decreased MCF7 and MBA-DA-231 breast cell proliferation, while it reversed by hypoxia inducible factor 1α (HIF1α). Knockdown of NRF2 inhibited glycolysis by decreasing the expression of genes participated in glucose metabolism, including HK2, PFKFB3, PKM2 and LDHA. Our results further indicated that the AKT activation and AMPK inhibition were required for NRF2-mediated up-regulation of glycolytic enzymes. Consistent with these results, a positive correlation existed between NRF2 or HIF1α and several key glycolytic genes in human breast cancer cell samples and breast cancer patients with high NRF2 or HIF1α expression had poorer overall survival. In conclusion, our study demonstrates that NRF2 promotes breast cancer progression by enhancing glycolysis through coactivation of HIF1α, implicating that NRF2 is a potential molecular target for breast cancer treatment.