Prostate Cancer Coverage from Every Angle

SIRT3 Expression in Metastasis of Prostate Cancer to the Bone

By: Lauren Harrison, MS
Posted: Tuesday, December 22, 2020

Researchers from the Roswell Park Cancer Center determined that the mitochondrial enzyme aconitase is altered in prostate cancer cells, potentially allowing aggressive prostate cancer to metastasize to the bone in the setting of increased lipid synthesis. Subhamoy Dasgupta, PhD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, and colleagues published their findings in Cancer Research.

“This is an early-stage discovery identifying potential pathways that could be targeted to block prostate tumor growth inside the bone,” said Dr. Dasgupta in an institutional press release.

The team utilized prostate cancer cell lines to perform gene-deletion studies utilizing the CRISPR-Cas9 system to highlight the role aconitase plays in prostate cancer cells. Aconitase was noted to be present in higher levels among cell androgen receptor–positive cells compared with androgen receptor–negative cells.

Mitochondrial aconitase is a tricarboxylic acid cycle enzyme that serves to facilitate citrate metabolism. There were significantly reduced levels of lipids in cells deficient of aconitase in comparison to wild-type cells, indicating the enzyme’s possible role in lipogenesis. Its functioning in cancer cells was noted to be dependent on LYS2258 acetylation, which was reversibly regulated by sirtuin 3, a mitochondrial protein predominantly expressed in prostate cancer cells.

Steroid receptor coactivator-2 (SRC2) binding to the androgen receptor forms a repressive complex through recruitment of histone deacetylase 2 to the sirtuin 3 promoter, according to the researchers. Depletion of the SRC2 enhanced sirtuin 3 expression and reduced acetylated aconitase.

The investigators also performed xenograft experiments in mice to monitor for development of bone metastases under a variety of conditions. The results showed that in human prostate tumors, aconitase activity was significantly elevated. There was also increased expression of SRC2 and reduction in sirtuin 3 in metastatic prostate cancer lesions. With suppression of SRC2, sirtuin 3 was reactivated, which was enough to inhibit prostate cancer colonization to the bone microenvironment.

Disclosure: For a full list of authors’ disclosures, visit

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