Key enzyme is missing from triple-negative breast cancer

Triple-negative breast cancer cells are missing a key enzyme that other cancer cells contain. A recent study at the Markey Cancer Center in Kentucky provides insight into potential therapeutic targets to treat aggressive cancer. The study is unique as it comes from the only laboratory in the country to specifically study the metabolic process of triple-negative breast cancer cells.

Triple-negative breast cancer is the most deadly subtype of breast cancer, and tends to occur in women at a younger age. This subtype of breast cancer has poor clinical outcomes due to the early metastasis of tumor cells, resistance to chemotherapy, and the lack of specific drugs that target it. Identifying this change in the cancer's metabolic process provides major insight into developing drugs to target the disease, according to the researchers. 

Normally, all cells, including cancerous cells, use glucose to initiate the process of making adenosine-5'-triphosphate (ATP) for fuel to carry out essential functions. This process, called glycolysis, leads to other processes that use oxygen to make higher quantities of ATP. However, solid tumor cells, which have little access to oxygen, are forced to rely almost exclusively on aerobic glycolysis for survival.  

This study, led by Peter Zhou, MD, PhD, of the University of Kentucky Markey Cancer Center and published in Cancer Cell (2013; doi:10.1016/j.ccr.2013.01.022), showed that the powerful transcription factor complex Snail-G9a-Dnmt1 is over-expressed in triple-negative breast cancer, inhibiting the enzyme 1,6-bisphosphate. The loss of this enzyme shuts down the glucose anabolic pathway and promotes the glucose catabolic pathway, leading to a large amount of glucose entering the tumor cells and thus feeding the aggressive cancer. The metabolic switch empowers triple-negative breast cancer cells to suck more glucose from the body, increasing macromolecule biosynthesis in tumor cells and maintaining ATP production despite a dearth of nutrients and an oxygen-free environment.

"These findings present significant insights regarding the development and progression of triple-negative breast cancer," said Zhou. "They indicate that targeting the metabolic alteration will lead to an effective approach for treating this deadly disease."

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