Interleukin 6 enhances glycolysis through expression of the glycolytic enzymes hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3.
Enhanced glycolysis is important for oncogenesis and for the survival and proliferation of cancer cells in the tumor microenvironment. Recent studies have also shown that proinflammatory cytokine signaling, such as that mediated by nuclear factor kappaB and signal transducer and activator of transcription 3 (STAT3), is important for the generation of inflammation-associated tumors. However, the link between inflammation and enhanced glycolysis has not been identified. In the present study, we found that the proinflammatory cytokine interleukin (IL)-6 enhanced glycolysis in mouse embryonic fibroblasts and human cell lines. Moreover, STAT3 activated by IL-6 enhanced the expression of the glycolytic enzymes hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3). Ectopic expression of PFKFB3 enhanced glycolysis, suggesting that the IL-6-STAT3 pathway enhances glycolysis through the induction of these enzymes. Our findings may provide a novel mechanism for inflammation-associated oncogenesis.
Ando
Masaru
M
Department of Molecular Oncology, Graduate School of Medicine, Nippon Medical School.
Uehara
Ikuno
I
Kogure
Kayo
K
Asano
Yumi
Y
Nakajima
Wataru
W
Abe
Yoshinori
Y
Kawauchi
Keiko
K
Tanaka
Nobuyuki
N
D000818:Animals; D005347:Fibroblasts / Q000201:enzymology; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D056945:Hep G2 Cells; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics; D051379:Mice; D025481:Phosphofructokinase-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000172:deficiency / Q000235:genetics; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics; D015854:Up-Regulation
C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D011994:Recombinant Proteins; C498144:Rela protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D019344:Lactic Acid; D006593:Hexokinase; C107345:PFKFB3 protein, human; D025481:Phosphofructokinase-2; D005947:Glucose