GPD2: The relationship with cancer and neural stemness

Cells Dev. 2023 Mar:173:203824. doi: 10.1016/j.cdev.2022.203824. Epub 2022 Dec 31.

Abstract

We previously reported that knocking down GPD2 (glycerol-3-phosphate dehydrogenase 2), responsible for the glycerol-phosphate shuttle, causes human hepatocarcinoma-derived HuH-7 cells, lowering the cancer stemness. After examining whether GPD2 expression in the other cell lines could affect their cancer stemness, this study showed that human neuroblastoma-derived SH-SY5Y cells also lower the ability of sphere formation by knocking down GPD2. This suggests that GPD2 relates to the common mechanism for maintaining cancer stem cells, as in the cases like SH-SY5Y and HuH-7 cells. In addition, knocking down GPD2 in SH-SY5Y cells showed a morphological change and increasing tendency of neuronal marker genes, including GAP43, NeuN, and TUBB3, indicating that GPD2 may contribute to not only cancer but also neural stem cell maintenance. After all, GPD2 may play a role in maintaining cancer and neural stemness, although further rigorous studies are essential to conclude this. It is expected that GPD2 will be a novel target gene for cancer therapy, stem cell research, and development.

Keywords: ATP synthesis; Energy metabolism; GPD2; cancer stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular*
  • Glycerolphosphate Dehydrogenase / genetics
  • Glycerolphosphate Dehydrogenase / metabolism
  • Humans
  • Liver Neoplasms*
  • Neuroblastoma*

Substances

  • Glycerolphosphate Dehydrogenase
  • GPD2 protein, human