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Androgen stimulates glycolysis for de novo lipid synthesis by increasing the activities of hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 in prostate cancer cells

 Jong-Seok MOON  ;  Won-Ji JIN  ;  Jin-Hye KWAK  ;  Hyo-Jeong KIM  ;  Mi-Jin YUN  ;  Jae-Woo KIM  ;  Sahng Wook PARK  ;  Kyung-Sup KIM 
 BIOCHEMICAL JOURNAL, Vol.433(1) : 225-233, 2011 
Journal Title
Issue Date
Androgens/pharmacology* ; Cell Line, Tumor ; Glycolysis/drug effects* ; Hexokinase/metabolism* ; Humans ; Lipids/biosynthesis* ; Male ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphofructokinase-2/metabolism* ; Phosphorylation ; Promoter Regions, Genetic ; Prostatic Neoplasms/enzymology ; Prostatic Neoplasms/metabolism* ; Receptors, Androgen/metabolism ; Transcriptional Activation/drug effects ; Up-Regulation
androgen, glycolysis, hexokinase 2, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase ; 2 (PFKFB2), ; prostate cancer.
Up-regulation of lipogenesis by androgen is one of the most characteristic metabolic features of LNCaP prostate cancer cells. The present study revealed that androgen increases glucose utilization for de novo lipogenesis in LNCaP cells through the activation of HK2 (hexokinase 2) and activation of the cardiac isoform of PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase). Activation of PKA (cAMP-dependent protein kinase) by androgen increased phosphorylation of CREB [CRE (cAMP-response element)-binding protein], which in turn bound to CRE on the promoter of the HK2 gene resulting in transcriptional activation of the HK2 gene. Up-regulation of PFKFB2 expression was mediated by the direct binding of ligand-activated androgen receptor to the PFKFB2 promoter. The activated PI3K (phosphoinositide 3-kinase)/Akt signalling pathway in LNCaP cells contributes to the phosphorylation of PFKFB2 at Ser466 and Ser483, resulting in the constitutive activation of PFK-2 (6-phosphofructo-2-kinase) activity. Glucose uptake and lipogenesis were severely blocked by knocking-down of PFKFB2 using siRNA (small interfering RNA) or by inhibition of PFK-2 activity with LY294002 treatment. Taken together, our results suggest that the induction of de novo lipid synthesis by androgen requires the transcriptional up-regulation of HK2 and PFKFB2, and phosphorylation of PFKFB2 generated by the PI3K/Akt signalling pathway to supply the source for lipogenesis from glucose in prostate cancer cells.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Kim, Jae Woo(김재우) ORCID logo https://orcid.org/0000-0001-5456-9495
Moon, Jong-Seok(문종석)
Park, Sahng Wook(박상욱) ORCID logo https://orcid.org/0000-0002-9594-7074
Yun, Mi Jin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
Jin, Won Ji(진원지)
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