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[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.  

[​Author Information]

Jeon JY1, Lee H2, Park J2, Lee M1, Park SW1, Kim JS1, Lee M1, Cho B3, Kim K4, Choi AM5, Kim CK6, Yun M7.

1Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.

2Department of Clinical Nursing Science, Yonsei University College of Nursing, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.

3Division of Medical Oncology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.

4Department 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.

5Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY, USA.

6Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02026, USA. Electronic address: ckkim@bwh.harvard.edu.

7Department 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.