Researchers with the University of Pennsylvania School of Veterinary Medicine have demonstrated the process by which the cancer-causing chemical dioxin attacks the cellular machinery, disrupts normal cellular function and ultimately promotes tumor progression.
The team identified for the first time that mitochondria, the cellular sub-units that convert oxygen and nutrients into cellular fuel, are the target of tetrachlorodibenzodioxin, or TCDD. The study showed that TCDD induces mitochondria-to-nucleus stress signaling, which in turn induces the expression of cell nucleus genes associated with tumor promotion and metastasis.
The mechanism the research team has described is directly relevant to understanding incidences of breast and other cancers in human populations exposed to these chemicals. With a better understanding of this underlying cellular mechanism, researchers hope to improve their understanding of tumor growth and promotion.
"Now that we have identified this signaling mechanism we can look at ways to disrupt this complex chain of events,” said Narayah Avadhani, chair of the Department of Animal Biology at Penn's School of Veterinary Medicine and the study's lead investigator. “Our ultimate goal is to block the propagation of this mitochondrial stress signaling and inhibit the expression of the proteins that combine to assist cancer growth.”