Understanding how cancers cells reprogram cellular metabolic pathways is critical toward the development of novel therapeutic compounds. Cutting off a cancer cell’s “food supply” is a veritable lynchpin for the efficient removal of tumors and now researchers at the University of Texas MD Anderson Cancer Center believe they may have found a protein that serves that very function.
The scientists observed that a protein named 14-3-3σ was able to regulate the metabolic reprogramming of cancer cells and also serve to protect cells from the transformation into tumors.
“We know that all cancers grow by learning how to reprogram their metabolism,” said senior author Mong-Hong Lee, Ph.D., professor of molecular and cellular oncology at MD Anderson Cancer Center. “But exactly how this occurs has not been fully understood. Our study showed that 14-3-3σ opposes and reverses tumor-promoting metabolic programs.”
The findings from this study were published recently in Nature Communications through an article entitled “Cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming.”
14-3-3σ is part of a family of conserved regulatory molecules that are expressed in all eukaryotic cells. Moreover, the 14-3-3 proteins have been observed to be actively involved in regulating an array of signaling molecules such as kinases, phosphatases, and transmembrane receptors. 14-3-3σ has been shown previously to regulate cancer genes, such as p53 and suppress tumor growth, but in this instance the investigators were able to observe the protein acting on metabolic pathways and reversing tumorigenic signals.
Dr. Lee and his team showed that 14-3-3σ opposed tumor-promoting metabolic programs by increasing the degradation of the transcription factor c-Myc. Additionally, 14-3-3σ demonstrated a suppressive effect on cancer glycolysis, mitochondrial biogenesis, as well as a range of other major metabolic processes of tumors.
“14-3-3σ expression levels can help predict overall and recurrence-free survival rates, tumor glucose uptake, and metabolic gene expression in breast cancer patients,” explained Dr. Lee. “These results highlight that 14-3-3σ is an important regulator of tumor metabolism, and loss of 14-3-3σ expression is critical for cancer metabolic reprogramming.”
The MD Anderson team is excited about the findings from this new study and feels that it adds extended insight into the connective pathways between the cell cycle and cancer cell metabolism.
“We anticipate that pharmacologically elevating 14-3-3σ's function in tumors could be a promising direction for targeted anti-cancer metabolism therapy development in the future,” concluded Dr. Lee.