Sept. 11 (UPI) -- A protein associated with BRCA was found to act as a tumor-suppressing gene by regulating cell death in several cancers, potentially paving the way for new treatment options, according to a study.
Researchers at The University of Texas MD Anderson Cancer Center found that BRCA, which stands for for BReast CAncer susceptibility gene, was associated with the cell death called ferroptosis in the kidney, eye, bile duct, mesothelioma, or thin layer of tissue, and other cancers, Their findings were published Monday in the journal Nature Cell Biology.
The gene was identified as BAP1.
When the BRCA1 or BRCA2 genes are mutated, DNA damage may not be repaired properly, according to the National Cancer Institute. Cells are more likely to develop additional genetic alterations that can lead to cancer.
"Although BAP1 is frequently mutated or deleted in a variety of cancers, the process by which it suppresses tumors remains unclear," Dr. Boyi Gan, associate professor in Department of Experimental Radiation Oncology at Texas, said in a press release. "Our study achieved a comprehensive identification of BAP1-regulated target genes and relevant biological processes in cancer cells, and identified a BAP1-mediated epigenetic mechanism linking ferroptosis to tumor suppression."
Ferroptosis, which is distinct from other forms of regulated cell death, is caused by depletion of cystine. The amino acid is vital to cancer cell growth and survival, as well as overproduction of molecular oxygen carriers in lipids.
"It is well established that cell death, most notably apoptosis, plays important roles in tumor suppression," Gan said. "The roles of and regulatory mechanisms of ferroptosis in tumor biology, however, still remain largely unexplored."
In their research, they found BAP1 produces a key enzyme that interacts with other enzymes and cellular components to regulate genes.
Similar cancer cells that do not express BAP1 were not affected.
In addition, the researchers found BAP1 promotes ferroptosis by mediating repression of a cystine "transporter" called SLC7A11.
"We showed that BAP1 inhibits tumor development partly through SLC7A11 and ferroptosis and that cancer-associated BAP1 mutants lose their abilities to repress SLC7A11 and to promote ferroptosis," Gan said. "Together, our results uncover a previously unappreciated mechanism coupling ferroptosis to tumor suppression."