Key protein in prostate cancer energy production identified

Tg expression of TRAP1 accelerates prostate tumorigenesis

Scientists at The Wistar Institute have demonstrated how a protein called TRAP1 is an important driver of prostate cancer and appears to be a valuable therapeutic target for the disease.

TRAP1 is an important regulator of energy production in healthy and cancerous cells. The findings are published in the Journal of Biological Chemistry.

Mitochondria are known as the powerhouse of the cells because of their role in energy production.

In recent years, research has shown that different tumors are able to manipulate genes and proteins responsible for energy production in order to help them survive.

TRAP1 is a chaperone protein that is structurally similar to heat shock protein 90 (HSP90), which is found in larger amounts in the mitochondria of cancer cells.

In a prior study, researchers bred mice with the TRAP1 protein “knocked out” to determine what impact it may have on disease.

These special mice lived longer and experienced fewer age-related illnesses, suggesting that the protein played an important role in disease.

In this study, instead of removing the TRAP1 protein, the team generated mice with the TRAP1 protein overexpressed.

Additionally, the mice were bred to lose one copy of the PTEN gene, which is an important tumor suppressor gene.

At least one copy of PTEN is deleted in about 40 percent of cases of prostate cancer and is often found in more aggressive tumors, so mice without this gene more accurately simulate the behavior of the disease.

The combination of increased TRAP1 coupled with the loss of PTEN resulted in aggressive, early-onset invasive prostate cancer, according to the study.

The researchers found increased tumor cell proliferation, inhibition of apoptosis (a form of programmed cell death that is thought to halt the progression of tumor cells), and increased epithelial cell invasion.

These findings suggest that TRAP1 has a role in promoting the mitochondrial “fitness” of a prostate tumor, making it more aggressive and less responsive to treatment.

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Citation: Lisanti S, et al. (2016). Transgenic Expression of Mitochondrial Chaperone TRAP1 Accelerates Prostate Cancer Development. Journal of Biological Chemistry, published online. DOI: 10.1074/jbc.M116.745950.
Figure legend: This image is credited to Lisanti S, et al.