title: MAF1 suppresses AKT-mTOR signaling and liver cancer through activation of PTEN transcription.
abstract: The phosphatidylinositol 3-kinase/phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase/protein kinase B/mammalian target of rapamycin (PI3K-PTEN-AKT-mTOR) pathway is a central controller of cell growth and a key driver for human cancer. MAF1 is an mTOR downstream effector and transcriptional repressor of ribosomal and transfer RNA genes. MAF1 expression is markedly reduced in hepatocellular carcinomas, which is correlated with disease progression and poor prognosis. Consistently, MAF1 displays tumor-suppressor activity toward in vitro and in vivo cancer models. Surprisingly, blocking the synthesis of ribosomal and transfer RNAs is insufficient to account for MAF1's tumor-suppressor function. Instead, MAF1 down-regulation paradoxically leads to activation of AKT-mTOR signaling, which is mediated by decreased PTEN expression. MAF1 binds to the PTEN promoter, enhancing PTEN promoter acetylation and activity.
  
  
  
  In contrast to its canonical function as a transcriptional repressor, MAF1 can also act as a transcriptional activator for PTEN, which is important for MAF1's tumor-suppressor function. These results have implications in disease staging, prognostic prediction, and AKT-mTOR-targeted therapy in liver cancer. (Hepatology 2016;63:1928-1942).
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Rutgers Cancer Institute of New Jersey and Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, NJ.
authors.forename: Chi Kwan
authors.initials: CK
authors.lastname: Tsang
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Suihai
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Liwu
authors.initials: L
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.|Rutgers Cancer Institute of New Jersey and Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, NJ.
authors.forename: Hui-Yun
authors.initials: HY
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.|Rutgers Cancer Institute of New Jersey and Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, NJ.
authors.forename: X F Steven
authors.initials: XF
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C520535:MAF1 protein, human; C529453:Maf1 protein, mouse; D012097:Repressor Proteins; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase