Researchers from Rice University Center for Theoretical Biological Physics (CTBP), the University of North Texas, Denton (UNT), the University of California, San Diego (UCSD) and the Hebrew University of Jerusalem, identified two proteins as prime suspects in the proliferation of breast cancer. The study appeared in the Proceedings of the National Academy of Sciences’ Online Early Edition, suggesting the potentiality of the two proteins as therapeutic targets to slow or stop tumor growth.
The pair of proteins NAF-1 and mitoNEET are referred to as NEETs. NEET proteins transport iron molecules or iron sulfur clusters inside cells. The proteins naturally exist on the outer surface of the mitochondria, the power plant that supplies cells with chemical energy. Mitochondria also play a role in a cell’s life cycle, including its death.
The team of José Onuchic, CTBP co-director, a biological physicist at Rice, was originally researching the structure and the function of mitoNEET, and the team recognized a connection between NEETs and reduced rates of breast cancer among women who take a diabetes drug that targets mitoNEET. “NEET proteins play a key role in the overall stress response of cells,” Onuchic said. “Anytime you stress a system, these proteins are there to help, but in cases where cells are overcome by stress, NEETs can become highly overexpressed. That’s what drew our interest in a potential connection to cancer.”
He further commented: “What’s interesting about these two proteins is that mitoNEET is always on the surface of the mitochondria membrane, while NAF-1 is on the mitochondria and the endoplasmic reticulum,” Onuchic said. “A lot of messaging rolls between these two proteins. You have to affect both of them to stop proliferation.”
In the study, reserchers found an overabundance of both mitoNEET and NAF-1 in breast cancer cells. Moreover, the team found a direct correlation between NEET protein levels and the overall progression of the disease. The results suggest that the overabundance of NEETs is a factor enhancing cancer cell growth, and that NEETs could be a prime target for anticancer drugs.
“Developing drugs that target important cellular pathways that are specific for cancer cells is perhaps the most important goal of anticancer therapy,” said Ron Mittler, Professor at Department of Biological Sciences, University of North Texas. “Historically, mitochondrial pathways have largely been overlooked, but our results indicate that these are important pathways and that targeting the NEET proteins could have a significant effect.”
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