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Study links BAP1 protein to tumor suppression in kidney, eye, bile duct and mesothelioma cancers

Date:
September 10, 2018
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
Researchers have shown how BRCA-associated protein 1 (BAP1) serves as a tumor suppressor gene in kidney, eye, bile duct, mesothelioma and other cancers by regulating a form of cell death called ferroptosis, opening up a potential new area of therapy research.
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Researchers at The University of Texas MD Anderson Cancer Center have shown how BRCA-associated protein 1 (BAP1) serves as a tumor suppressor gene in kidney, eye, bile duct, mesothelioma and other cancers by regulating a form of cell death called ferroptosis, opening up a potential new area of therapy research. Findings from the study, led by Boyi Gan, Ph.D., associate professor, Department of Experimental Radiation Oncology, were published in the Sept. 10 online issue of Nature Cell Biology.

"Although BAP1 is frequently mutated or deleted in a variety of cancers, the process by which it suppresses tumors remains unclear," said Gan. "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 is a recently identified form of regulated cell death caused by depletion of cystine, an amino acid vital to cancer cell growth and survival, and by overproduction of molecular carriers of oxygen known as reactive oxygen species (ROS) on lipids, which have been linked to cancer and are targets of some therapies.

"Ferroptosis is structurally, genetically and biochemically distinct from other forms of regulated cell death such as apopotosis," said Gan. "It is well established that cell death, most notably apoptosis, plays important roles in tumor suppression. The roles of and regulatory mechanisms of ferroptosis in tumor biology, however, still remain largely unexplored."

Gan's team described how BAP1 encodes a key enzyme which interacts with other enzymes and cellular components to regulate genes, resulting in tumor suppression via ferroptosis. The researchers found that treatment with a ROS inducer resulted in substantially more ferropotosis-related cell death in BAP1 cancer cells than in other similar cancer cells which do not express BAP1. They also discovered that 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," said Gan. "Together, our results uncover a previously unappreciated mechanism coupling ferroptosis to tumor suppression."


Story Source:

Materials provided by University of Texas M. D. Anderson Cancer Center. Note: Content may be edited for style and length.


Journal Reference:

  1. Yilei Zhang, Jiejun Shi, Xiaoguang Liu, Li Feng, Zihua Gong, Pranavi Koppula, Kapil Sirohi, Xu Li, Yongkun Wei, Hyemin Lee, Li Zhuang, Gang Chen, Zhen-Dong Xiao, Mien-Chie Hung, Junjie Chen, Peng Huang, Wei Li, Boyi Gan. BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nature Cell Biology, 2018; DOI: 10.1038/s41556-018-0178-0

Cite This Page:

University of Texas M. D. Anderson Cancer Center. "Study links BAP1 protein to tumor suppression in kidney, eye, bile duct and mesothelioma cancers." ScienceDaily. ScienceDaily, 10 September 2018. <www.sciencedaily.com/releases/2018/09/180910142453.htm>.
University of Texas M. D. Anderson Cancer Center. (2018, September 10). Study links BAP1 protein to tumor suppression in kidney, eye, bile duct and mesothelioma cancers. ScienceDaily. Retrieved March 27, 2024 from www.sciencedaily.com/releases/2018/09/180910142453.htm
University of Texas M. D. Anderson Cancer Center. "Study links BAP1 protein to tumor suppression in kidney, eye, bile duct and mesothelioma cancers." ScienceDaily. www.sciencedaily.com/releases/2018/09/180910142453.htm (accessed March 27, 2024).

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