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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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

Fingerprint

regulators
Tumors
Cell Cycle
tumors
cancer
Cells
cycles
metabolism
Neoplasms
Metabolism
glycolysis
biological evolution
gene expression
Gene expression
glucose
breast
Neoplastic Cell Transformation
therapy
degradation
Ubiquitination

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., ... 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

The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming. / Phan, Liem; Chou, Ping Chieh; Velazquez-Torres, Guermarie; Samudio, Ismael; Parreno, Kenneth; Huang, Yaling; Tseng, Chieh; Vu, Thuy; Gully, Chris; Su, Chun Hui; Wang, Edward; Chen, Jian; Choi, Hyun Ho; Fuentes-Mattei, Enrique; Shin, Ji Hyun; Shiang, Christine; Grabiner, Brian; Blonska, Marzenna; Skerl, Stephen; Shao, Yiping; Cody, Dianna; Delacerda, Jorge; Kingsley, Charles; Webb, Douglas; Carlock, Colin; Zhou, Zhongguo; Hsieh, Yun Chih; Lee, Jaehyuk; Elliott, Andrew; Ramirez, Marc; Bankson, Jim; Hazle, John; Wang, Yongxing; Li, Lei; Weng, Shaofan; Rizk, Nibal; Wen, Yu Ye; Lin, Xin; Wang, Hua; Wang, Huamin; Zhang, Aijun; Xia, Xuefeng; Wu, Yun; Habra, Mouhammed; Yang, Wei; Pusztai, Lajos; Yeung, Sai Ching; Lee, Mong Hong.

In: Nature Communications, Vol. 6, 7530, 16.07.2015.

Research output: Contribution to journalArticle

Phan, L, Chou, PC, Velazquez-Torres, G, Samudio, I, Parreno, K, Huang, Y, Tseng, C, Vu, T, Gully, C, Su, CH, Wang, E, Chen, J, Choi, HH, Fuentes-Mattei, E, Shin, JH, Shiang, C, Grabiner, B, Blonska, M, Skerl, S, Shao, Y, Cody, D, Delacerda, J, Kingsley, C, Webb, D, Carlock, C, Zhou, Z, Hsieh, YC, Lee, J, Elliott, A, Ramirez, M, Bankson, J, Hazle, J, Wang, Y, Li, L, Weng, S, Rizk, N, Wen, YY, Lin, X, Wang, H, Wang, H, Zhang, A, Xia, X, Wu, Y, Habra, M, Yang, W, Pusztai, L, Yeung, SC & Lee, MH 2015, 'The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming', Nature Communications, vol. 6, 7530. https://doi.org/10.1038/ncomms8530
Phan L, Chou PC, Velazquez-Torres G, Samudio I, Parreno K, Huang Y et al. The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming. Nature Communications. 2015 Jul 16;6. 7530. https://doi.org/10.1038/ncomms8530
Phan, Liem ; Chou, Ping Chieh ; Velazquez-Torres, Guermarie ; Samudio, Ismael ; Parreno, Kenneth ; Huang, Yaling ; Tseng, Chieh ; Vu, Thuy ; Gully, Chris ; Su, Chun Hui ; Wang, Edward ; Chen, Jian ; Choi, Hyun Ho ; Fuentes-Mattei, Enrique ; Shin, Ji Hyun ; Shiang, Christine ; Grabiner, Brian ; Blonska, Marzenna ; Skerl, Stephen ; Shao, Yiping ; Cody, Dianna ; Delacerda, Jorge ; Kingsley, Charles ; Webb, Douglas ; Carlock, Colin ; Zhou, Zhongguo ; Hsieh, Yun Chih ; Lee, Jaehyuk ; Elliott, Andrew ; Ramirez, Marc ; Bankson, Jim ; Hazle, John ; Wang, Yongxing ; Li, Lei ; Weng, Shaofan ; Rizk, Nibal ; Wen, Yu Ye ; Lin, Xin ; Wang, Hua ; Wang, Huamin ; Zhang, Aijun ; Xia, Xuefeng ; Wu, Yun ; Habra, Mouhammed ; Yang, Wei ; Pusztai, Lajos ; Yeung, Sai Ching ; Lee, Mong Hong. / The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming. In: Nature Communications. 2015 ; Vol. 6.
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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.",
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AU - Phan, Liem

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AU - Parreno, Kenneth

AU - Huang, Yaling

AU - Tseng, Chieh

AU - Vu, Thuy

AU - Gully, Chris

AU - Su, Chun Hui

AU - Wang, Edward

AU - Chen, Jian

AU - Choi, Hyun Ho

AU - Fuentes-Mattei, Enrique

AU - Shin, Ji Hyun

AU - Shiang, Christine

AU - Grabiner, Brian

AU - Blonska, Marzenna

AU - Skerl, Stephen

AU - Shao, Yiping

AU - Cody, Dianna

AU - Delacerda, Jorge

AU - Kingsley, Charles

AU - Webb, Douglas

AU - Carlock, Colin

AU - Zhou, Zhongguo

AU - Hsieh, Yun Chih

AU - Lee, Jaehyuk

AU - Elliott, Andrew

AU - Ramirez, Marc

AU - Bankson, Jim

AU - Hazle, John

AU - Wang, Yongxing

AU - Li, Lei

AU - Weng, Shaofan

AU - Rizk, Nibal

AU - Wen, Yu Ye

AU - Lin, Xin

AU - Wang, Hua

AU - Wang, Huamin

AU - Zhang, Aijun

AU - Xia, Xuefeng

AU - Wu, Yun

AU - Habra, Mouhammed

AU - Yang, Wei

AU - Pusztai, Lajos

AU - Yeung, Sai Ching

AU - Lee, Mong Hong

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N2 - 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.

AB - 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.

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