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GPD2: The relationship with cancer and neural stemness
Maimaiti Mikeli1, Makoto Fujikawa2, Tsutomu Tanabe1
1Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
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.
Insights
Knocking down glycerol-3-phosphate dehydrogenase 2 (GPD2) reduces cancer stemness in liver and neuroblastoma cells. GPD2 may maintain both cancer and neural stem cells, offering a potential therapeutic target.
Area of Science:
- Biochemistry
- Cancer Biology
- Stem Cell Research
Background:
- Glycerol-3-phosphate dehydrogenase 2 (GPD2) is crucial for the glycerol-phosphate shuttle.
- Previous studies linked GPD2 knockdown to reduced cancer stemness in hepatocarcinoma cells.
Purpose of the Study:
- To investigate the role of GPD2 in maintaining cancer stemness in other cell lines.
- To explore GPD2's potential involvement in neural stem cell maintenance.
Main Methods:
- Knockdown of GPD2 in human hepatocarcinoma (HuH-7) and neuroblastoma (SH-SY5Y) cell lines.
- Assessment of sphere formation ability to evaluate cancer stemness.
- Analysis of morphological changes and expression of neuronal marker genes (GAP43, NeuN, TUBB3) in SH-SY5Y cells.
Main Results:
- GPD2 knockdown reduced sphere formation in both HuH-7 and SH-SY5Y cells, indicating decreased cancer stemness.
- Knocking down GPD2 in SH-SY5Y cells induced morphological changes and increased expression of neuronal markers.
- These findings suggest GPD2 is involved in maintaining both cancer and neural stemness.
Conclusions:
- GPD2 plays a role in the common mechanism for maintaining cancer stem cells.
- GPD2 may also contribute to neural stem cell maintenance.
- GPD2 represents a potential novel target for cancer therapy and stem cell research.
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