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

Autor: Phan L; 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., Chou PC; 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., Velazquez-Torres G; 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., Samudio I; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Parreno K; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Huang Y; 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., Tseng C; 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., Vu T; 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., Gully C; 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., Su CH; 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., Wang E; 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., Chen J; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Choi HH; 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., Fuentes-Mattei E; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Shin JH; 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., Shiang C; 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., Grabiner B; 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., Blonska M; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Skerl S; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Shao Y; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Cody D; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Delacerda J; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Kingsley C; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Webb D; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Carlock C; 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., Zhou Z; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Hsieh YC; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lee J; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Elliott A; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Ramirez M; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Bankson J; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Hazle J; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wang Y; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Li L; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Weng S; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Rizk N; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wen YY; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lin X; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wang H; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wang H; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Zhang A; Methodist Hospital Research Institute, Houston, TX 77030, USA., Xia X; Methodist Hospital Research Institute, Houston, TX 77030, USA., Wu Y; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Habra M; Department of Endocrinology Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Yang W; Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Pusztai L; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Yeung SC; 1] Department of Endocrinology Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [2] Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lee MH; 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.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2015 Jul 16; Vol. 6, pp. 7530. Date of Electronic Publication: 2015 Jul 16.
DOI: 10.1038/ncomms8530
Abstrakt: 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.
Databáze: MEDLINE