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Nodal promotes glioblastoma cell growth
Tanya De Silva1, Gang Ye, Yao-Yun Liang
1Department of Biology, York University Toronto, ON, Canada.
Abstract:
Nodal is a member of the transforming growth factor-β (TGF-β) superfamily that plays critical roles during embryogenesis. Recent studies in ovarian, breast, prostate, and skin cancer cells suggest that Nodal also regulates cell proliferation, apoptosis, and invasion in cancer cells. However, it appears to exert both tumor-suppressing and tumor-promoting effects, depending on the cell type. To further understand the role of Nodal in tumorigenesis, we examined the effect of Nodal in glioblastoma cell growth and spheroid formation using U87 cell line. Treatment of U87 with recombinant Nodal significantly increased U87 cell growth. In U87 cells stably transfected with the plasmid encoding Nodal, Smad2 phosphorylation was strongly induced and cell growth was significantly enhanced. Overexpression of Nodal also resulted in tight spheroid formation. On the other hand, the cells stably transfected with Nodal siRNA formed loose spheroids. Nodal is known to signal through activin receptor-like kinase 4 (ALK4) and ALK7 and the Smad2/3 pathway. To determine which receptor and Smad mediate the growth promoting effect of Nodal, we transfected siRNAs targeting ALK4, ALK7, Smad2, or Smad3 into Nodal-overexpressing cells and observed that cell growth was significantly inhibited by ALK4, ALK7, and Smad3 siRNAs. Taken together, these findings suggest that Nodal may have tumor-promoting effects on glioblastoma cells and these effects are mediated by ALK4, ALK7, and Smad3.
Insights
Nodal signaling promotes glioblastoma cell growth and tight spheroid formation. This tumor-promoting effect in U87 cells is mediated by activin receptor-like kinase 4 (ALK4), ALK7, and Smad3.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Nodal, a transforming growth factor-β (TGF-β) superfamily member, is crucial in embryogenesis.
- Nodal's role in cancer is complex, showing both tumor-suppressing and tumor-promoting effects depending on cell type.
- Its function in glioblastoma tumorigenesis remains largely unexplored.
Purpose of the Study:
- To investigate the impact of Nodal on glioblastoma cell growth and spheroid formation.
- To identify the specific signaling pathways and receptors mediating Nodal's effects in glioblastoma.
Main Methods:
- Utilized U87 glioblastoma cell line for experiments.
- Administered recombinant Nodal and employed stable transfection with Nodal-encoding plasmids and Nodal siRNA.
- Assessed cell growth, Smad2 phosphorylation, and spheroid formation.
- Used siRNAs targeting ALK4, ALK7, Smad2, and Smad3 to elucidate signaling pathways.
Main Results:
- Recombinant Nodal and Nodal overexpression significantly enhanced U87 cell growth.
- Nodal overexpression led to the formation of tight spheroids, while Nodal siRNA resulted in loose spheroids.
- Inhibition of ALK4, ALK7, and Smad3 significantly reduced cell growth in Nodal-overexpressing cells.
Conclusions:
- Nodal exhibits tumor-promoting effects in glioblastoma cells.
- The growth-promoting effects of Nodal in glioblastoma are mediated through the activin receptor-like kinase 4 (ALK4), ALK7, and Smad3 signaling pathway.
