2020
Knockout of sulfatase 2 is associated with decreased steatohepatitis and fibrosis in a mouse model of nonalcoholic fatty liver disease
Kim TH, Banini BA, Asumda FZ, Campbell NA, Hu C, Moser CD, Shire AM, Han S, Ma C, Krishnan A, Mounajjed T, White TA, Gores GJ, LeBrasseur NK, Charlton MR, Roberts LR. Knockout of sulfatase 2 is associated with decreased steatohepatitis and fibrosis in a mouse model of nonalcoholic fatty liver disease. AJP Gastrointestinal And Liver Physiology 2020, 319: g333-g344. PMID: 32683952, PMCID: PMC7509257, DOI: 10.1152/ajpgi.00150.2019.Peer-Reviewed Original ResearchConceptsFast food dietStandard chow dietWT miceDiet-induced steatohepatitisNonalcoholic steatohepatitisSulfatase 2Hepatic fibrosisMouse modelStandard chow diet ad libitumChow diet ad libitumNonalcoholic fatty liver diseaseDiet-induced mouse modelConditions of overnutritionProtein expressionFatty liver diseasePotential therapeutic mechanismWild-type miceDiet ad libitumThreefold increaseLiver diseaseChow dietKO miceLiver fibrosisSteatohepatitisMurine modelThe extracellular sulfatase SULF2 promotes liver tumorigenesis by stimulating assembly of a promoter-looping GLI1-STAT3 transcriptional complex
Carr RM, Romecin Duran PA, Tolosa EJ, Ma C, Oseini AM, Moser CD, Banini BA, Huang J, Asumda F, Dhanasekaran R, Graham RP, Toruner MD, Safgren SL, Almada LL, Wang S, Patnaik MM, Roberts LR, Fernandez-Zapico ME. The extracellular sulfatase SULF2 promotes liver tumorigenesis by stimulating assembly of a promoter-looping GLI1-STAT3 transcriptional complex. Journal Of Biological Chemistry 2020, 295: 2698-2712. PMID: 31988246, PMCID: PMC7049957, DOI: 10.1074/jbc.ra119.011146.Peer-Reviewed Original ResearchConceptsGLI family zinc finger 1Transcriptional complexTarget genesSer/ThrSTAT3 target genesSULF2 overexpressionZinc finger 1Suppressor of cytokineTyrosine kinase 4Promoter conformationSpecific gene signaturesSTAT3 functionHuman orthologPromoter bindingTranscriptomic analysisConsensus sitesGli1 knockdownTransgenic mice overexpressingSignal transducerTranscription 3Molecular mechanismsFinger 1Kinase 4Hepatocellular carcinoma growthOverexpression
2017
Transcriptional Induction of Periostin by a Sulfatase 2–TGFβ1–SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma
Chen G, Nakamura I, Dhanasekaran R, Iguchi E, Tolosa EJ, Romecin PA, Vera RE, Almada LL, Miamen AG, Chaiteerakij R, Zhou M, Asiedu MK, Moser CD, Han S, Hu C, Banini BA, Oseini AM, Chen Y, Fang Y, Yang D, Shaleh HM, Wang S, Wu D, Song T, Lee JS, Thorgeirsson SS, Chevet E, Shah VH, Fernandez-Zapico ME, Roberts LR. Transcriptional Induction of Periostin by a Sulfatase 2–TGFβ1–SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma. Cancer Research 2017, 77: 632-645. PMID: 27872089, PMCID: PMC5429157, DOI: 10.1158/0008-5472.can-15-2556.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorBlotting, WesternCarcinoma, HepatocellularCell Adhesion MoleculesChromatin ImmunoprecipitationEnzyme-Linked Immunosorbent AssayGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansImmunohistochemistryKaplan-Meier EstimateLiver NeoplasmsMiceMice, KnockoutNeovascularization, PathologicOligonucleotide Array Sequence AnalysisReal-Time Polymerase Chain ReactionSignal TransductionSmad ProteinsSulfatasesSulfotransferasesTransforming Growth Factor beta1ConceptsHepatocellular carcinomaSulfatase 2Protein periostinMicrovascular densityHCC cellsExtracellular matrix protein periostinTGFβ1/Smad pathwayMetastatic hepatocellular carcinomaLower microvascular densityPoor patient survivalWild-type miceClinical HCC specimensHuman HCC cellsPatient survivalPOSTN levelsAntiangiogenic approachesKO miceRational drug developmentParacrine fashionNumerous tumorsHCC angiogenesisTumor growthEndothelial proliferationTumor angiogenesisHCC specimens