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Research identifies enzyme very important to the metastatic development of prostate most cancers cells

While prostate cancer originates in the prostate, metastasis, or spread of a tumor from its original site to other organs, remains one of the leading causes of death in people with the disease. Prostate tumors can metastasize to a number of different organs, including the liver, lymph nodes, and bones.

People with advanced prostate cancer often develop bone metastases -; Prostate cancer lesions growing on distant bones -; these are very painful and difficult to treat.

Given the significant differences between the microenvironments that surround the bone and prostate, a team from Roswell Park Comprehensive Cancer Center set out to learn more about how prostate tumors survive and grow in bone.

Under the direction of Dr. Subhamoy Dasgupta, assistant professor of oncology in the Cell Stress Biology Department at Roswell Park, the team found that prostate tumors alter their metabolism to produce more fats that help them survive in the bones.

The team’s results were published online in Cancer Research, a journal of the American Association for Cancer Research.

Data from this study suggest that a mitochondrial enzyme called aconitase plays a key role in the development and viability of prostate cancer cells. The Roswell Park research team discovered that prostate tumors can change their metabolism and produce extra fats by stimulating this enzyme.

“There is a fundamental gap in our knowledge of how prostate tumor cells survive in bone,” explains Dr. Dasgupta, senior author of the new work. “In this study, we provide evidence that prostate tumor cells alter their mitochondrial metabolism to increase the synthesis of fats, which act as a kind of food source and allow prostate cells to take root and survive in a new place.”

The team reports that aconitase activation is made possible by suppressing a deacetylase enzyme called sirtuin-3 or SIRT3, which leads to increased lipid synthesis.

Previous studies have linked increased expression of another protein, SRC-2, to aggressive prostate cancer. In the current study, Dr. Dasgupta and colleagues found that patients with high SRC-2 in their tumors also showed low levels of SIRT3 expression, which helped these aggressive tumors to spread to new sites.

Through their pre-clinical work in the laboratory, the researchers showed that the loss of SRC-2 significantly reduced the metastatic growth of prostate cancer cells in the bone microenvironment.

The team’s results underscore the importance of mitochondrial metabolic adaptation for the growth of advanced bone metastatic prostate cancer and suggest that blocking SRC-2 to improve SIRT3 expression may be a viable treatment strategy.

“This is an early discovery that identifies potential pathways that could target and block the growth of prostate tumors in the bone,” notes Dr. Dasgupta. “We have started additional work to investigate the clinical utility of our research results and to identify certain drugs or new active substances that could block this pathway.”


Roswell Park Comprehensive Cancer Center

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