Metabolic reprogramming by PCK1 promotes TCA cataplerosis, oxidative stress and apoptosis in liver cancer cells and suppresses hepatocellular carcinoma

• Published in: Oncogene Vol. 37; no. 12; pp. 1637 - 1653
• Main Authors: Liu, Meng-Xi, Jin, Lei, Sun, Si-Jia, Liu, Peng, Feng, Xu, Cheng, Zhou-Li, Liu, Wei-Ren, Guan, Kun-Liang, Shi, Ying-Hong, Yuan, Hai-Xin, Xiong, Yue
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2018; Nature Publishing Group
• Subjects: 101/58; 13/1; 13/31; 14/105; 14/63; 38/77; 42/109; 631/67; 631/80; 64/60; 82/51; 96/2; Animals; Apoptosis; Apoptosis - genetics; Blood glucose; Cancer; Cancer cells; Cancer genetics; Carcinoma; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Biology; Cell death; Cell proliferation; Cells (Biology); Cells, Cultured; Cellular Reprogramming - genetics; Citric Acid Cycle - genetics; Colon; Energy shortages; Gene expression; Genes; Genes, Tumor Suppressor - physiology; Genetic aspects; Gluconeogenesis; Gluconeogenesis - genetics; Glucose; HEK293 Cells; Hep G2 Cells; Hepatocellular carcinoma; Hepatocytes; Human Genetics; Humans; Internal Medicine; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - physiology; Isoforms; Ketoglutaric acid; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mammalian cells; MCF-7 Cells; Medicine; Medicine & Public Health; Metabolism; Mice; Mice, Inbred ICR; Mice, Nude; Mitochondria; Oncology; Oxidative stress; Oxidative Stress - genetics; Patients; Phosphates; Phosphoenolpyruvate Carboxykinase (GTP) - genetics; Phosphoenolpyruvate Carboxykinase (GTP) - physiology; Reactive oxygen species; Rodents; Skin; Therapeutic applications; Tumor cell lines; Tumorigenesis; Tumors

Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting step in hepatic gluconeogenesis pathway to maintain blood glucose levels. Mammalian cells express two PCK genes, encoding for a cytoplasmic (PCPEK-C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectivel...