Related Experiment Videos
Do cancer cells die because of Nogo-B?
Thomas Oertle1, Doron Merkler, Martin E Schwab
1Brain Research Institute, University of Zurich and Department of Biology, ETH Zurich, Switzerland. oertlle@hio.unizh.ch
Abstract:
Nogo-A is a potent neurite outgrowth inhibitory protein in vitro and is suggested to play a role in the lack of regeneration in the central nervous system of adult higher vertebrates. A shorter splice isoform, ASY/Nogo-B, has recently been reported to act as a proapoptotic protein, the loss of which would be typical for cancer cells. Here, we show that the osteosarcoma cell line SaOS-2 and the cell line CHO do express high levels of endogenous Nogo-B and that stable transfectants overexpressing high levels of Nogo-B do not differ significantly from the respective parental wild-type or control cell lines both in respect to cell proliferation and to spontaneous apoptosis or cell death induced by staurosporine and tunicamycin. The deletion of the second transmembrane domain of Nogo-B, which has been claimed to abolish its proapoptotic activity, leads to a shift of the protein from the ER to a cytoplasmic localization, suggesting that ER stress of highly overexpressed Nogo-B may lead to aversive cellular reactions under particular conditions. Our data do not support a function of Nogo-B as a physiological pro-apoptotic protein in certain types of cancer.
Insights
Nogo-B, a protein suggested to induce cancer cell death, does not significantly affect cell proliferation or apoptosis in osteosarcoma and CHO cells. Its localization, not its expression, may influence cellular reactions under stress.
Area of Science:
- Neuroscience
- Cell Biology
- Cancer Research
Background:
- Nogo-A inhibits neurite outgrowth, impacting central nervous system regeneration.
- Nogo-B, a splice isoform, was proposed as a pro-apoptotic protein relevant to cancer cells.
Purpose of the Study:
- To investigate the role of Nogo-B in cancer cell proliferation and apoptosis.
- To determine if Nogo-B functions as a physiological pro-apoptotic protein in cancer.
Main Methods:
- Analysis of Nogo-B expression in SaOS-2 and CHO cell lines.
- Assessment of cell proliferation and apoptosis in Nogo-B overexpressing cells.
- Evaluation of cell death induced by staurosporine and tunicamycin.
- Investigation of a Nogo-B mutant lacking the second transmembrane domain.
Main Results:
- SaOS-2 and CHO cells express high levels of endogenous Nogo-B.
- Overexpression of Nogo-B did not significantly alter cell proliferation or spontaneous apoptosis.
- Nogo-B overexpression did not increase sensitivity to staurosporine or tunicamycin-induced cell death.
- Deletion of the second transmembrane domain caused Nogo-B to shift from the ER to the cytoplasm, potentially inducing ER stress.
Conclusions:
- The data do not support Nogo-B's function as a physiological pro-apoptotic protein in the studied cancer cell types.
- ER stress, potentially induced by mislocalized Nogo-B, might cause cellular reactions under specific conditions.