Department of ICT Environmental Health System, Graduate School, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
Department of ICT Environmental Health System, Graduate School, Soonchunhyang University, Asan-si, 31538, Republic of Korea; Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-si, 31538, Republic of Korea.
Biochem Biophys Res Commun. 2020 Dec 17;533(4):1378-1384. doi: 10.1016/j.bbrc.2020.10.025. Epub 2020 Oct 21.
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.
格林-1（GREM1）是骨形态发生蛋白（BMPs）的拮抗剂之一，最近有报道称其在多种癌症中过表达，包括乳腺癌。GREM1 参与肿瘤促进，但关于其在癌细胞糖酵解中的作用知之甚少。在这项研究中，我们研究了 GREM1 在乳腺癌细胞糖酵解中的作用及其潜在的分子机制。我们首先观察到 GREM1 过表达的乳腺癌细胞葡萄糖摄取和乳酸生成增加。GREM1 增加了己糖激酶-2（HK2）的表达，HK2 催化葡萄糖的磷酸化，这是糖酵解的第一步。此外，GREM1 通过 ROS-Akt 信号通路激活 STAT3 转录因子。GREM1 激活的 ROS-Akt-STAT3 轴通过增加乳腺癌细胞中 HK2 的表达参与促进葡萄糖摄取。因此，我们的研究表明，GREM1 通过增加乳腺癌细胞中的糖酵解参与乳腺癌的促进，这是一种新的机制。
