The ‘Achilles heel’ of one of the most commonly affected genes in cancer has been identified, opening the door to potential new cancer therapies.
Researchers at Cold Spring Harbor Laboratory (CSHL) in the US have discovered a new function for a molecule called Importin-11 as a potential protector of a commonly affected protein in cancer called PTEN.
PTEN acts as a guardian protein that stops cells from growing uncontrollably. To prevent the protein from being overly active and preventing any cell growth at all, PTEN is transported into cells, labelled with other proteins, and destroyed by internal cell machinery.
In many cancers, PTEN is present in low levels, however, the gene does not have to be mutated to result in this effect – an anomaly whose cause has remained unknown until now.
The US team discovered that Importin-11 acts as a shield against the destruction of PTEN in cells by creating mouse models where the Importin-11 gene was deleted. In these mice, PTEN levels were lower than normal whilst lung and prostate cancers were common.
Testing samples of lung cancer patient tumours where the Importin-11 was deleted showed similar low levels of PTEN. In prostate cancer, Importin-11’s deletion correlated with higher rates of disease relapse and metastasis in patients who had had their prostate removed.
“We think that the degradation of PTEN after loss or impairment of Importin-11 is a very effective driver of human prostate cancer,” said CSHL associate professor Lloyd Trotman. “Our results suggest that Importin-11 is the ‘Achilles’ heel’ of the ubiquitination system that maintains the correct levels of PTEN inside cells.”