Phosphatase and tensin homolog (or “Pten” for short), is a tumor suppressor that is deficient in around 20 to 25 percent of cancer sufferers. Researchers from the Mayo Clinic recently found that Pten safeguards against tumor formation by keeping chromosome numbers optimal when a cell splits in two, leaving the body with two daughter cells in its place.
During the study, the final three amino acids of the Pten protein were discovered to be completely missing. These acids are crucial because they are what help to form a mitotic spindle. This spindle is a structure that is needed in order for proper chromosome segregation to take place. The complete study can be seen online in Nature Cell Biology journal.
Other than p53, Pten is the most common human tumor suppressor. Researchers believe that the Pten’s phosphatase activity is what counteracts Pl3 kinase activity. When this function is lost, tumor formation is begun as enzymes (called AKT) are stimulated on an uncontrolled level. When this happens, cell proliferation as well as survival is hyperactive, making them more difficult to remove. It has remained a question for a very long time whether or not Pten damage in cancer patients could in fact lead to cell chromosomes being placed in a completely new order, similar to when you shuffle a deck of cards.
The latest study has found that Pten localizes itself to mitotic spindle poles in order to recruit the protein EG5. EG5 pushes the poles apart in order to create a symmetrical bipolar spindle that disconnects duplicate chromosomes. The research team discovered that the recruitment process involved Dlg1, which is an Eg5-binding protein that attaches itself to the last three Pten amino acids at spindle poles. Mutant mice that do not have these amino acids were found to have a disproportionate number of chromosomes, which led to tumors forming very rapidly.
Researchers believe their latest findings predict that a massive proportion of Pten tumors will be sensitive to Eg5-inhibiting drugs. This opens up a whole new door of opportunities in the world of cancer therapy. Once there is a proper target set in place, improved treatment is typically right around the bend.