Gremlin-1 activates Akt/STAT3 signaling, which increases the glycolysis rate in breast cancer cells

被引：19
作者：
Kim, Na Hui [1 ]
Sung, Nam Ji [1 ]
Youn, Hyung-Sun [1 ,2 ]
Park, Sin-Aye [1 ,2 ]
机构：
[1] Soonchunhyang Univ, Grad Sch, Dept ICT Environm Hlth Syst, Asan 31538, South Korea
[2] Soonchunhyang Univ, Coll Med Sci, Dept Biomed Lab Sci, Asan 31538, South Korea
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2020年 / 533卷 / 04期
基金：
新加坡国家研究基金会;
关键词：
GREM1; Breast cancer; Glycolysis; HK2; STAT3; EPITHELIAL-MESENCHYMAL TRANSITION; EXPRESSION; GROWTH; CARCINOMA;
D O I：
10.1016/j.bbrc.2020.10.025
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Gremlin-1 (GREM1), one of the antagonists of bone morphogenetic proteins (BMPs), has recently been reported to be overexpressed in a variety of cancers including breast cancer. GREM1 is involved in tumor promotion, but little is known about its role in the glycolysis of cancer cells. In this study, we investigated the role of GREM1 in glycolysis of breast cancer cells and its underlying molecular mechanisms. We first observed that glucose uptake and lactate production were increased in GREM1-overexpressing breast cancer cells. GREM1 increased the expression of hexokinase-2 (HK2), which catalyzes the phosphorylation of glucose, the first step in glycolysis. In addition, GREM1 activated STAT3 transcription factor through the ROS-Akt signaling pathway. The ROS-Akt-STAT3 axis activated by GREM1 was involved in promoting glucose uptake by increasing the expression of HK2 in breast cancer cells. Therefore, our study suggested a new mechanism by which GREM1 is involved in breast cancer promotion by increasing glycolysis in breast cancer cells. (C) 2020 Elsevier Inc. All rights reserved.
引用
收藏
页码：1378 / 1384
页数：7
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