The protein Importin-11 may protect men from developing prostate cancer by preventing the degradation of the tumor-suppressor protein PTEN, according to recent research.
Loss of Importin-11 resulted in the development of lung and prostate cancers in animal models and predicted disease recurrence and progression to metastasis in prostate cancer patients undergoing radical prostatectomy.
The study, “The nuclear transport receptor Importin-11 is a tumor suppressor that maintains PTEN protein,” was published in The Journal of Cell Biology. It sheds light on the mechanisms underlying the development of PTEN-associated cancers, and may lead to new treatment approaches.
PTEN, a protein that prevents cells from growing uncontrollably, is mutated in many different types of cancers. Certain cancer patients show low levels of the PTEN protein, even when both PTEN genes are normal.
Researchers at Cold Spring Harbor Laboratory in New York sought to examine the workings of PTEN nuclear import, which could be protecting this protein from degradation.
They found that Importin-11 protects PTEN by both transporting it into the nucleus of the cell and in its physical separation from elements of the protein degradation machinery. Loss of Importin-11 in lab dishes and in animal models resulted in increased PTEN degradation and the development of lung cancers and prostate tumors.
The findings could explain the link between Importin-11 mutations and the development of lung cancer. The researchers stressed that loss of Importin-11 may account for nearly one-third of PTEN-deficient lung cancers.
“Given a population of 409,000 patients with lung cancer in the U.S. alone, [more than] 60,000 of them would fall into the category in which PTEN function might be restored by interfering with degradation,” they wrote.
In human prostate cancer, the team also found that deletion of Importin-11 was associated with a high risk of relapse, assessed as an increase in PSA levels, after radical prostatectomy. In addition, prostate cancer patients with a loss of Importin-11 were also at increased risk of metastasis.
“We therefore infer that the degradation of PTEN protein observed after loss and impairment of Importin-11 is a very effective driver of human prostate cancer progression,” the researchers wrote.
This suggests that interfering with PTEN degradation could be a promising approach to treat patients with lung, prostate, and other cancers who do not exhibit PTEN mutations but have lower levels of the protein.