Mechanism of Tumor Suppressor Discovered

Researchers in a recent study discovered that phosphate and tensin homolog (Pten) is able to protect against tumors by keeping chromosome numbers intact during cell division.

Pten is a known tumor suppressor that is defective in 20 to 25% of all patients with cancer. Researchers found that the last 3 amino acids of Pten are crucial for forming an intact mitotic spindle required for accurate chromosome segregation, according to a study published by Nature Cell Biology.

The protein Pten is thought to prevent PI3 kinase activity through its phosphate activity. Without the prevention of PI3 kinase activity, tumor formation begins due to uncontrolled AKT stimulation.

AKT is typically overactive in tumors since it can stimulate cell proliferation and survival, according to the study.

"We found that Pten localizes to mitotic spindle poles to recruit the 'motor' protein EG5, which moves the poles apart to form a perfectly symmetrical bipolar spindle that accurately separates duplicated chromosomes," said senior author Jan van Deursen, PhD.

The researchers then found that this process involves Dlg1, which is a protein that binds to Eg5 and docks to the last 3 Pten amino acids at spindle poles. They discovered that mice without these amino acids have atypical chromosome numbers and a high occurrence of tumors.

The findings suggest that Pten tumors will be sensitive to Eg5-inhibiting drugs, providing a new target for treatment.