Can protein 14-3-3 sigma prevent or kill breast cancer tumors?

MD Anderson study shows potential of simple molecule in cancer metabolism

MD Anderson News Release 07/15/2015

Every parent knows the maxim “feed a cold, starve a fever.” In cancer, however, exactly how to feed or starve a tumor has not been easy to determine.

A study led by scientists at The University of Texas MD Anderson Cancer Center has shown that a simple molecule called 14-3-3 sigma could be one answer for explaining cancer metabolism, the chemical process by which a tumor forms, grows or dies. 

“We know that all cancers grow by learning how to reprogram their metabolism,” said Mong-Hong Lee, Ph.D., professor of Molecular and Cellular Oncology. “But exactly how this occurs has not been fully understood. Our study showed that 14-3-3 sigma opposes and reverses tumor-promoting metabolic programs.” 

Lee’s study results, which appear in the July 16, 2015 issue of Nature Communications, revealed new understanding about how 14-3-3 sigma – a cell cycle “controller” –regulates cancer metabolic programming, thus protecting healthy cells from turning into tumor-producing factories.

In vivo and in vitro experiments showed that, among many biochemical effects, 14-3-3 sigma suppresses cancer glycosis, which prevents cancer’s ability to convert glucose into pyruvate, a substance essential for cell growth.

“14-3-3 sigma expression levels can help predict overall and recurrence-free survival rates, tumor glucose uptake, and metabolic gene expression in breast cancer patients,” said Lee. “These results highlight that 14-3-3 sigma is an important regulator of tumor metabolism, and loss of 14-3-3 sigma expression is critical for cancer metabolic reprogramming.”

Lee believes that the study findings provide additional insight about the “crosstalk” between cancer metabolism and cell cycle.

“We anticipate that pharmacologically elevating 14-3-3 sigma’s function in tumors could be a promising direction for targeted anti-cancer metabolism therapy development in the future,” he said.

MD Anderson study team participants included Liem Phan, Ph.D., Ping-Chieh Chou, Ph.D., Guermarie Velazquez-Torres, Ph.D., Ismael Samudio, M.D., Kenneth Parreno, Yaling Huang, Ph.D., Chieh Tseng, Thuy Vu, Ph.D., Chris Gully, Ph.D., Chun-Hui Su, Ph.D., Edward Wang, Ph.D., Jian Chen, M.D., Ph.D., Hyun-Ho Choi, Ph.D., Enrique Fuentes-Mattei, Ph.D., Ji-Hyun Shin, Ph.D., Christine Shiang, Brian Grabiner, Ph.D., Marzenna Blonska, Ph.D., Stephen Skerl, Yiping Shao, Ph.D., Dianna Cody, Ph.D., Jorge Delacerda, Charles Kingsley, Douglas Webb, Colin Carlock, Zhongguo Zhou, M.D., Ph.D., Yun-Chi Hseih, Ph.D., Jaehyuk Lee, Ph.D., Andrew Elliott, Ph.D., Marc Ramirez, Ph.D., Jim Bankson, Ph.D., John Hazle, Ph.D., Yongxing Wang, Ph.D., Lei Li, Ph.D., Shaofan Weng, Nibal Rizk, M.D., Yu Ye Wen, Ph.D., Mouhammed Habra, M.D., Wei Yang, M.D., Lajos Pusztai, M.D., D.Phil., and Sai-Ching Yeung, M.D., Ph.D.

The study was funded by the National Institutes of Health/National Cancer Institute (CA016672, T32CA009299, R25TCA57730, and RO1CA089266), the Cancer and Prevention Research Institute of Texas (RP101243-P5), the U.S. Department of Defense (W81XWH-10-0171), the Fidelity Foundation, the Susan G. Komen for the Cure, the Vietnam Education Foundation, and the Rosalie B. Hite Fund for Cancer Research Fellowship.