are known as the powerhouse of the cells because of their role in energy
production, and 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, which is found in larger amounts in the mitochondria of cancer cells.’
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, Dario C. Altieri, M.D., president and CEO of The Wistar
Institute, director of The Wistar Institute Cancer Center, the Robert &
Penny Fox Distinguished Professor, and colleagues 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.
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," Altieri said.
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."
study, instead of removing the TRAP1 protein, the Altieri laboratory 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.
combination of increased TRAP1 coupled with the loss of PTEN resulted in
aggressive, early-onset invasive prostate cancer, according to the study.
Altieri and colleagues 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.
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