title: The regulation of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase by autophagy in low-glycolytic hepatocellular carcinoma cells.
abstract: The glycolytic phenotype is a dominant metabolic phenomenon in cancer and is reflected in becoming aggressive. Certain hepatocellular carcinoma lack increased glycolysis and prefer to uptake acetate than glucose for metabolism. Autophagy plays a role in preserving energies and nutrients when there is limited external nutrient supply and maintains glucose level of blood though supporting gluconeogenesis in the liver. As the role of autophagy and gluconeogenesis in HCC following the glycolic activity was not clear, we cultured HCC cells with different glycolytic levels in Hank's balanced salt solution (HBSS) to induce autophagy and conducted the activity of gluconeogenesis. Both autophagy and gluconeogenesis were induced in low glycolytic HCC cells (HepG2). In glycolytic Hep3B cells, only autophagy without gluconeogenesis was induced upon starvation. When autophagy was blocked, the level of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) was reduced in HepG2 cells and not in Hep3B. Altogether, we investigated contribution of hepatic gluconeogenesis to the metabolic phenotype of HCC cells and the role of autophagy as a potential mechanism regulating gluconeogenesis in low glycolytic HCC.
authors.affiliation: Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
authors.forename: Jeong Yong
authors.initials: JY
authors.lastname: Jeon
authors.affiliation: Department of Clinical Nursing Science, Yonsei University College of Nursing, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
authors.forename: Hyangkyu
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Clinical Nursing Science, Yonsei University College of Nursing, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
authors.forename: Jeayeo
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
authors.forename: Misu
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
authors.forename: Sae Whan
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
authors.forename: Ji Sook
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
authors.forename: Milim
authors.initials: M
authors.lastname: Lee
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
authors.forename: Byoungchul
authors.initials: B
authors.lastname: Cho
authors.affiliation: Department of Biochemistry and Molecular Biology, Brain Korea 21 Project for Medical Science, Institute of Genetic Science, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
authors.forename: Kyungsup
authors.initials: K
authors.lastname: Kim
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY, USA.
authors.forename: Augustine M K
authors.initials: AM
authors.lastname: Choi
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02026, USA. Electronic address: ckkim@bwh.harvard.edu.
authors.forename: Chun K
authors.initials: CK
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea. Electronic address: yunmijin@yuhs.ac.
authors.forename: Mijin
authors.initials: M
authors.lastname: Yun
mesh_terms: D001343:Autophagy; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005943:Gluconeogenesis; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D006019:Glycolysis; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism*; D013217:Starvation / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D005952:Glucose-6-Phosphatase; C000597251:PCK2 protein, human; D019764:Phosphoenolpyruvate Carboxykinase (ATP)
keywords: Autophagy; Gluconeogenesis; Glycolysis; Hepatocellular carcinoma; Starvation