The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming

Liem Phan, Ping Chieh Chou, Guermarie Velazquez-Torres, Ismael Samudio, Kenneth Parreno, Yaling Huang, Chieh Tseng, Thuy Vu, Chris Gully, Chun Hui Su, Edward Wang, Jian Chen, Hyun Ho Choi, Enrique Fuentes-Mattei, Ji Hyun Shin, Christine Shiang, Brian Grabiner, Marzenna Blonska, Stephen Skerl, Yiping ShaoDianna Cody, Jorge Delacerda, Charles Kingsley, Douglas Webb, Colin Carlock, Zhongguo Zhou, Yun Chih Hsieh, Jaehyuk Lee, Andrew Elliott, Marc Ramirez, Jim Bankson, John Hazle, Yongxing Wang, Lei Li, Shaofan Weng, Nibal Rizk, Yu Ye Wen, Xin Lin, Hua Wang, Huamin Wang, Aijun Zhang, Xuefeng Xia, Yun Wu, Mouhammed Habra, Wei Yang, Lajos Pusztai, Sai Ching Yeung, Mong Hong Lee

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Abstract

Extensive reprogramming of cellular energy metabolism is a hallmark of cancer. Despite its importance, the molecular mechanism controlling this tumour metabolic shift remains not fully understood. Here we show that 14-3-3σ regulates cancer metabolic reprogramming and protects cells from tumorigenic transformation. 14-3-3σ opposes tumour-promoting metabolic programmes by enhancing c-Myc poly-ubiquitination and subsequent degradation. 14-3-3σ demonstrates the suppressive impact on cancer glycolysis, glutaminolysis, mitochondrial biogenesis and other major metabolic processes of tumours. Importantly, 14-3-3σ expression levels predict overall and recurrence-free survival rates, tumour glucose uptake and metabolic gene expression in breast cancer patients. Thus, these results highlight that 14-3-3σ is an important regulator of tumour metabolism, and loss of 14-3-3σ expression is critical for cancer metabolic reprogramming. We anticipate that pharmacologically elevating the function of 14-3-3σ in tumours could be a promising direction for targeted anticancer metabolism therapy development in future.

Original languageEnglish (US)
Article number7530
JournalNature Communications
Volume6
DOIs
StatePublished - Jul 16 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Phan, L., Chou, P. C., Velazquez-Torres, G., Samudio, I., Parreno, K., Huang, Y., Tseng, C., Vu, T., Gully, C., Su, C. H., Wang, E., Chen, J., Choi, H. H., Fuentes-Mattei, E., Shin, J. H., Shiang, C., Grabiner, B., Blonska, M., Skerl, S., ... Lee, M. H. (2015). The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming. Nature Communications, 6, [7530]. https://doi.org/10.1038/ncomms8530