title: EZH2 couples pancreatic regeneration to neoplastic progression.
abstract: Although the polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) is well recognized for its role as a key regulator of cell differentiation, its involvement in tissue regeneration is largely unknown. Here we show that EZH2 is up-regulated following cerulein-induced pancreatic injury and is required for tissue repair by promoting the regenerative proliferation of progenitor cells. Loss of EZH2 results in impaired pancreatic regeneration and accelerates KRas(G12D)-driven neoplasia. Our findings implicate EZH2 in constraining neoplastic progression through homeostatic mechanisms that control pancreatic regeneration and provide insights into the documented link between chronic pancreatic injury and an increased risk for pancreatic cancer.
authors.affiliation: Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Mallen-St Clair
authors.forename: Rengin
authors.initials: R
authors.lastname: Soydaner-Azeloglu
authors.forename: Kyoung Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Laura
authors.initials: L
authors.lastname: Taylor
authors.forename: Alexandra
authors.initials: A
authors.lastname: Livanos
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Pylayeva-Gupta
authors.forename: George
authors.initials: G
authors.lastname: Miller
authors.forename: Raphaël
authors.initials: R
authors.lastname: Margueron
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
authors.forename: Dafna
authors.initials: D
authors.lastname: Bar-Sagi
mesh_terms: D000681:Amylases / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000293:injuries / Q000502:physiology*; D063151:Polycomb Repressive Complex 2; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D000681:Amylases