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.

Gremlin-1（GREM1）是骨形态发生蛋白（BMP）的一种拮抗剂，最近有报道在包括乳腺癌在内的多种癌症中均过表达。GREM1参与肿瘤的促进，但对其在癌细胞的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。我们首先观察到在过度表达GREM1的乳腺癌细胞中葡萄糖的摄取和乳酸的产生增加。GREM1增加了己糖激酶-2（HK2）的表达，该酶催化糖酵解的第一步是葡萄糖的磷酸化。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HK2的表达来促进葡萄糖的摄取。因此，我们的研究提出了一种新的机制，通过该机制，GREM1通过增加乳腺癌细胞中的糖酵解而参与促进乳腺癌。