Wild-Type p53 Promotes Cancer Metabolic Switch by Inducing PUMA-Dependent Suppression of Oxidative Phosphorylation

• Published in: Cancer cell Vol. 35; no. 2; pp. 191 - 203.e8
• Main Authors: Kim, Jinchul, Yu, Lili, Chen, Wancheng, Xu, Yanxia, Wu, Meng, Todorova, Dilyana, Tang, Qingshuang, Feng, Bingbing, Jiang, Lei, He, Jingjin, Chen, Guihua, Fu, Xuemei, Xu, Yang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.02.2019
• Subjects: A549 Cells; Animals; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Proliferation; Glycolysis; HCT116 Cells; HeLa Cells; Hep G2 Cells; Humans; I-kappa B Kinase - metabolism; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; mitochondria; Mitochondria, Liver - metabolism; Mitochondria, Liver - pathology; Mitochondrial Membrane Transport Proteins - metabolism; mitochondrial pyruvate carrier; Monocarboxylic Acid Transporters - metabolism; Oxidative Phosphorylation; p53; Prognosis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; PUMA; Pyruvic Acid - metabolism; Signal Transduction; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; mitochondrial pyruvate carrier; PUMA; mitochondria; oxidative phosphorylation; glycolysis; p53

The tumor suppressor p53 is somatically mutated in half of all human cancers. Paradoxically, the wild-type p53 (WTp53) is often retained in certain human cancers, such as hepatocarcinoma (HCC). We discovered a physiological and oncogenic role of WTp53 in suppressing pyruvate-driven oxidative phospho...