Prostate cancer is a complicated and multi-headed beast, and doctors are constantly looking for any new edge, and new weapon that science can provide. Scientists at The Wistar Institute were not able to contribute a new bullet to The Cause – but they did find a new Achilles' heel at which to shoot.
It's called TRAP1, and it's a protein. The Wistar team learned that prostate cancer counts on it – a lot. They knew that various tumors are able to manipulate genes and proteins responsible for energy production in order to help them survive.
TRAP1 is a “chaperone” protein that resembles another protein which is found in larger amounts in the mitochondria of cancer cells. That was their first clue. So Wistar scientists bred mice with the TRAP1 protein "knocked out" to determine what impact it may have on disease. These TRAP1-less mice lived longer and experienced fewer age-related illnesses, which suggested to the researchers that the protein played an important role in disease.
"In our prior study, while we had evidence that hinted at TRAP1's role in tumor growth, we lacked the direct evidence we needed to define the role of this protein in prostate cancer development," said Dario C. Altieri, MD, president and CEO of The Wistar Institute and director of The Wistar Institute Cancer Center. "As we better understand the role of mitochondria in cancer, it's important to thoroughly study the roles of the proteins involved in helping tumors receive the energy they desire for survival."
In this new study, the scientists reversed the process. Wistar generated mice with the TRAP1 protein overexpressed, and with a gene that is a known tumor suppressor removed.
The combination of increased TRAP1 coupled with the loss of the suppressor gene resulted in aggressive, early-onset invasive prostate cancer. 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. The data suggest that TRAP1 has a role in promoting the mitochondrial "fitness" of a prostate tumor: it makes it more aggressive and less responsive to treatment.
"What is exciting about these findings is the fact that we believe TRAP1 is a druggable target," Altieri said. "We are continuing to advance our promising research and development program aimed at targeting the mitochondria in tumors."
The research has been published in The Journal of Biological Chemistry.