Publication Date:
2012-08-28
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534962/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534962/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yi, Wen -- Clark, Peter M -- Mason, Daniel E -- Keenan, Marie C -- Hill, Collin -- Goddard, William A 3rd -- Peters, Eric C -- Driggers, Edward M -- Hsieh-Wilson, Linda C -- R01 GM084724/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Aug 24;337(6097):975-80. doi: 10.1126/science.1222278.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22923583" target="_blank"〉PubMed〈/a〉
Keywords:
Acetylglucosamine/metabolism
;
Acylation
;
Adenosine Triphosphate/metabolism
;
Animals
;
Cell Hypoxia
;
Cell Line
;
Cell Line, Tumor
;
*Cell Proliferation
;
Glucose/*metabolism
;
Glycolysis
;
Glycosylation
;
Humans
;
Lactic Acid/metabolism
;
Mice
;
Mice, Nude
;
N-Acetylglucosaminyltransferases/genetics/metabolism
;
NADP/metabolism
;
Neoplasms/*metabolism/*pathology
;
Pentose Phosphate Pathway
;
Phosphofructokinase-1, Liver Type/antagonists & inhibitors/chemistry/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
