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.
authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
authors.forename: Liem
authors.identifier: 000000031194216X
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authors.lastname: Phan
authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
authors.forename: Ping-Chieh
authors.initials: PC
authors.lastname: Chou
authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
authors.forename: Guermarie
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authors.lastname: Velazquez-Torres
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ismael
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authors.lastname: Samudio
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
authors.forename: Yaling
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authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
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authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
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authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
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authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
authors.forename: Chun-Hui
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authors.lastname: Su
authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
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authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
authors.forename: Hyun-Ho
authors.initials: HH
authors.lastname: Choi
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Enrique
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authors.lastname: Fuentes-Mattei
authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Shin
authors.affiliation: 1] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA. [2] Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.lastname: Shiang
authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
authors.forename: Brian
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authors.lastname: Grabiner
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.lastname: Blonska
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yiping
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authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Dianna
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authors.lastname: Cody
authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.lastname: Delacerda
authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.lastname: Kingsley
authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
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authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Zhongguo
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authors.lastname: Zhou
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yun-Chih
authors.initials: YC
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authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jaehyuk
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authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Andrew
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authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.identifier: 000000028574154X
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authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xin
authors.identifier: 0000000309563654
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authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Methodist Hospital Research Institute, Houston, TX 77030, USA.
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authors.affiliation: Methodist Hospital Research Institute, Houston, TX 77030, USA.
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authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yun
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authors.affiliation: Department of Endocrinology Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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authors.forename: Sai-Ching
authors.initials: SC
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authors.affiliation: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX 77030, USA.
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mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D004734:Energy Metabolism / Q000235:genetics*; D005095:Exoribonucleases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D008875:Middle Aged; D001678:Organelle Biogenesis; D011379:Prognosis; D059748:Proteolysis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D054875:Ubiquitination / Q000235:genetics; D055815:Young Adult
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D005973:Glutamine; D005095:Exoribonucleases; C413442:SFN protein, human