title: The Role of PGC1α in Cancer Metabolism and its Therapeutic Implications.
abstract: PGC1α is a transcription factor coactivator that influences a majority of cellular metabolic pathways. Abnormal expression of PGC1α is associated with several chronic diseases and, in recent years, it has been shown to be a critical controller of cancer development. PGC1α acts as a stress sensor in cancer cells and can be activated by nutrient deprivation, oxidative damage, and chemotherapy. It influences mitochondria respiration, reactive oxygen species defense system, and fatty acid metabolism by interacting with specific transcription factors. The characteristic traits of PGC1α in maintaining metabolic homeostasis promote cancer cell survival and tumor metastasis in harsh microenvironments. Not only does PGC1α act as a coactivator, but is also itself controlled by oncogenes and transcription factors. PGC1α and these molecules can form signaling axes that include PML/PGC1α/PPARα, MITF/PGC1α, and PGC1α/ERRα, which are important in regulating metabolic adaptation in specific cancer types. Some of these PGC1α-associated pathways are inherently activated in cancer cells, and others are induced by stress, which enable cancer cells to acquire resistance against therapy. Notably, certain therapeutic-resistant cancer cells are addicted to PGC1α-dependent metabolic activities. Suppression of PGC1α expression resensitizes these cells to therapeutic treatments, which implicates PGC1α as a promising target in cancer molecular classification and therapy. Mol Cancer Ther; 15(5); 774-82. ©2016 AACR.
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Hunan, China. Key Laboratory of Chinese Ministry of Education, Central South University, Hunan, China. Key Laboratory of Carcinogenesis of Chinese Ministry of Public Health, Central South University, Hunan, China.
authors.forename: Zheqiong
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Hunan, China. Key Laboratory of Chinese Ministry of Education, Central South University, Hunan, China. Key Laboratory of Carcinogenesis of Chinese Ministry of Public Health, Central South University, Hunan, China.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Luo
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Hunan, China. Key Laboratory of Chinese Ministry of Education, Central South University, Hunan, China. Key Laboratory of Carcinogenesis of Chinese Ministry of Public Health, Central South University, Hunan, China.
authors.forename: Lanbo
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Hunan, China. Key Laboratory of Chinese Ministry of Education, Central South University, Hunan, China. Key Laboratory of Carcinogenesis of Chinese Ministry of Public Health, Central South University, Hunan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Hunan, China. Key Laboratory of Chinese Ministry of Education, Central South University, Hunan, China. Key Laboratory of Carcinogenesis of Chinese Ministry of Public Health, Central South University, Hunan, China. ycao98@vip.sina.com.
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha