The tumor-suppressing protein 14-3-3σ interferes with metabolic reprogramming that aids cancer growth and is therefore a potential target for anticancer metabolic therapy, according to a study led by researchers at The University of Texas MD Anderson Cancer Center.
“We know that all cancers grow by learning how to reprogram their metabolism,” said Mong-Hong Lee, Ph.D., a professor in the Department of Molecular and Cellular Oncology and the senior author of the study’s report. “Our study showed that 14-3-3σ opposes and reverses tumor-promoting metabolic programs.”
In breast cancer cell lines and in samples of tumor and normal breast tissues from breast cancer patients, Dr. Lee and colleagues found that 14-3-3σ regulated cellular energy metabolism, thus protecting healthy cells from metabolic reprogramming that supports tumorigenesis. By promoting the degradation of the proto-oncogene protein Myc, 14-3-3σ suppressed processes essential to this reprogramming, including glucose uptake, glycolysis, glutaminolysis, and mitochondrial biogenesis. The suppression of these processes by 14-3-3σ was demonstrated again in a mouse xenograft model.
Moreover, the loss of 14-3-3σ expression was found to result in tumor-promoting metabolic reprogramming. And low levels of 14-3-3σ were associated with shorter survival durations in the patients whose samples were used in the experiments.
“14-3-3σ expression levels can help predict overall and recurrence-free survival, tumor glucose uptake, and metabolic gene expression in breast cancer patients,” Dr. Lee said.
This relationship between 14-3-3σ and cancer metabolism could be harnessed to prevent tumors from growing. Although the complex role of 14-3-3σ in tumorigenesis is still not fully understood, the study’s findings could guide the design of new cancer treatments. “Pharmacologically elevating 14-3-3σ’s function in tumors could be a promising direction for targeted anticancer metabolism therapy development in the future,” Dr. Lee said.
This study’s report was published in Nature Communications in July.