The Role of 14-3-3 Sigma in Breast Cancer Metabolism

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A simple protein may be able to slow the growth or stop breast cancer growth altogether, according to a new study. The protein, called 14-3-3-sigma, is responsible for stopping and reversing cancer metabolism--the process by which tumors develop, grow, or die. 

This study was first published in the July 16, 2015 issue of Nature Communications. According to Liem Phan, PhD, first author on the article, the 14-3-3 sigma protein suppresses the effect on cancer glycolysis (prevents cancer’s ability to convert glucose into pyruvate), glutaminolysis (conversion of the amino acid glutamine to lactate), mitochondrial biogenesis (formation of new mitrochondria), and other major metabolic processes of tumors. Of note, this protein expression levels predict overall and recurrence-free survival rates, tumor glucose uptake, and metabolic gene expression in patients with breast cancer.¹

“We know that all cancers grow by learning how to reprogram their metabolism,” said Mong-Hong Lee, PhD, professor of Molecular and Cellular Oncology at The University of Texas MD Anderson Cancer Center in Houston.² Although how exactly this reprogramming happens is not entirely clear, this study shows that researchers are even closer to understanding the process.

The study helped the team gain new understanding about how 14-3-3 sigma – a cell cycle “controller” – regulates cancer metabolic programming, which prevents healthy cells from turning into tumor-producers, the hallmark of tumorigenesis.

In addition to generating the energy for cell division, tumor cells evade checkpoints that would normally block proliferation of abnormal tumor growth in the microenvironment. Tumor cells then reprogram their metabolic pathways to meet these needs during the process of tumor progression.³

Dr. Lee's research team anticipates that pharmacologically elevating the function of 14-3-3 sigma in tumors could work to enhance targeted anticancer metabolism therapy development in future.

References:

• Phan L, Chou PC, Velazquez-Torres G, et al. (2015). The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming. Nature Communications, Jul 16;6:7530.
• The University of Texas MD Anderson Cancer Center. (2015). Can protein 14-3-3 sigma prevent or kill breast cancer tumors?
• Cairns RA, Harris IS, Mak TW. (2011). Regulation of cancer cell metabolism. Nature Reviews, Feb;11(2):85-95.