Palma, December 6th, 2011. UIB and Lipopharma's scientists discover a third basic and critical requirement to transform a normal cell into a cancer cell.
Dr. Pablo Escriba, main promoter of Lipopharma, and his team of researchers at the University of the Balearic Islands (Spain) have discovered a new basic requirement to transform a normal cell into a cancer cell: the presence of very low membrane levels of sphingomyelin, a major phospholipid in the membrane of normal human cell membranes.
Until now it was know that the requirements for a normal cell to undergo tumorigenic transformation are: (1) activation of proto-oncogenes to oncogenes that produce altered proteins that accelerate cancer cell growth, and (2) inactivation of proteins produced by tumor suppressor genes (which normally act as repressors of this proliferation).
The type and number of oncogenes and tumor suppressor genes altered in a given cancer varies from cancer to cancer and from patient to patient. However, the new discovery shows that 100% of all human cancer cells studied until now exhibit low sphingomyelin levels. The work, that has been published today in the Proceedings of the National Academy of Sciences of the USA, highlights the relevance of this phenomenon, which could be connected with impairment of proliferation signals that occur at the membrane. Thus, sphingomyelin hampers the binding of certain oncogene products and shortcuts the proliferation signals sent to the cell nucleus to activate cancer cell division.
In normal cells, high sphingomyelin levels reduce the proliferative capacity of the cell, so that restoration of this situation in cancer cells would be a potential means to treat cancer. In fact, this study shows that the synthetic fatty acid, 2-hydroxyoleic acid, activates the enzyme sphigomyelin synthase (SMS)and restores membrane sphingomyelin to those levels found in normal cells. Not only is this compound the first SMS activator known but also a potent inhibitor of tumor growth. In fact, 2-hydroxyoleic acid has been designated orphan drug for the treatment of glioma (a type of severe brain cancer) by the European Medicines Agency, and clinical studies in patients will soon start to test its efficacy. In addition, these results further demonstrate that low sphingomyelin is the third basic requirement (in addition to oncogene activity and tumor suppressor gene product inactivation) to induce cancerand that this phenomenon is more important than the other requirements, as cancer cells reduce their proliferative capacity upon sphingomyelin restoration. Finally, this study will also open a new field in anticancer drug discovery, as SMS can be considered a new drug target in oncology and 2-hydroxyoleic acid the first specific and potent regulator of its activity.
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