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

Biochem Biophys Res Commun. 2020 Dec 17;533(4):1378-1384. doi: 10.1016/j.bbrc.2020.10.025. Epub 2020 Oct 21.

Abstract

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.

Keywords: Breast cancer; GREM1; Glycolysis; HK2; STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glucose / metabolism
  • Glycolysis / physiology*
  • Hexokinase / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Lactic Acid / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction*

Substances

  • GREM1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Reactive Oxygen Species
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Lactic Acid
  • HK2 protein, human
  • Hexokinase
  • Proto-Oncogene Proteins c-akt
  • Glucose