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 Shao; Dianna 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

doi:10.1038/ncomms8530

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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65 Scopus citations

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 language	English (US)
Article number	7530
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8530
State	Published - Jul 16 2015

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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, Article 7530. https://doi.org/10.1038/ncomms8530

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, HH, Fuentes-Mattei, E, Shin, J-H, 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, M-H 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

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title = "The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming",

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.",

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

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AU - Phan, Liem

AU - Chou, Ping-Chieh

AU - Velazquez-Torres, Guermarie

AU - Samudio, Ismael

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

PY - 2015/7/16

Y1 - 2015/7/16

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

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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