LA JOLLA, CA February 15, 2013 Doctors currently struggle to determine whether a breast tumor is likely to shift into an aggressive, life-threatening modean issue with profound implications for treatment. Now a group from The Scripps Research Institute (TSRI) has identified a mechanism through which mitochondria, the powerhouses of a cell, control tumor aggressiveness. Based on their findings, the team developed a simple treatment that inhibits cancer progression and prolongs life when tested in mice.
The research team, which describes its results February 15, 2013, in an article published online ahead of print by The Journal of Clinical Investigation, hopes to proceed quickly to human clinical trials to test this new approach using drugs already in use for other conditions.
Looking at Clues
The TSRI laboratory of Associate Professor Brunhilde H. Felding studies cancer, especially the mechanisms that control metastasis, the spread of cancer from its primary site to distant organs in the body.
Past research suggested that mutations affecting mitochondria, which are key to energy production in cells, strongly influence whether a tumor becomes aggressive. But the mechanism was not clear.
"We decided to investigate a specific protein complex, called mitochondrial complex I, that critically determines the energy output of cellular respiration," said the study's first author, Antonio F. Santidrian, a research associate in Felding's laboratory. To do this, the group teamed up with Akemi and Takao Yagi at TSRI, who are leading experts in complex I research. Using unique reagents from the Yagi group, the Felding team discovered that the balance of key metabolic cofactors processed by complex Ispecifically, nicotinamide adenine dinucleotide (NAD+) and NADH, the form it takes after accepting a key electron in the energy production cyclewas disturbed in aggressive breast cancer cells.
|Contact: Mika Ono|
Scripps Research Institute