期刊
SCIENCE
卷 337, 期 6097, 页码 975-980出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1222278
关键词
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资金
- National Institutes of Health [R01 GM084724]
- Department of Defense Breast Cancer Research Program [W81XWH-10-1-0988]
- Tobacco-Related Disease Research Program Postdoctoral Fellowship [19FT-0078]
- Agios Pharmaceuticals
Cancer cells must satisfy the metabolic demands of rapid cell growth within a continually changing microenvironment. We demonstrated that the dynamic posttranslational modification of proteins by O-linked beta-N-acetylglucosamine (O-GlcNAcylation) is a key metabolic regulator of glucose metabolism. O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway, thereby conferring a selective growth advantage on cancer cells. Blocking glycosylation of PFK1 at serine 529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo. These studies reveal a previously uncharacterized mechanism for the regulation of metabolic pathways in cancer and a possible target for therapeutic intervention.
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