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O‐GlcNAc Signaling Regulates Cancer Metabolism
Author(s) -
HsiehWilson Linda
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.452.2
Subject(s) - cancer cell , pentose phosphate pathway , microbiology and biotechnology , glycosylation , flux (metallurgy) , cell growth , signal transduction , biology , regulator , cancer , metabolic pathway , glycolysis , metabolism , biochemistry , chemistry , genetics , gene , organic chemistry
Cancer cells must satisfy the metabolic demands of rapid cell growth within a continually changing microenvironment. The dynamic post‐translational modification O ‐linked β‐ N ‐acetylglucosamine ( O ‐GlcNAc) couples nutrient sensing to the regulation of many important signaling pathways. We recently discovered that O ‐GlcNAc also serves as a key regulator of cellular metabolism itself and reprograms metabolic flux toward proliferative, pro‐survival pathways. Glycosylation was dynamically induced at Ser 529 of phosphofructokinase 1 (PFK1) under hypoxic conditions in rapidly dividing cancer cells. Glycosylation inhibited PFK1 activity and redirected glycolytic flux through the pentose phosphate pathway, thereby conferring a selective growth advantage to cancer cells. Blocking glycosylation of PFK1 at Ser529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo . Our studies reveal a novel mechanism for the regulation of metabolic pathways and suggest a new therapeutic approach to combat cancer.