title: Liver serine palmitoyltransferase activity deficiency in early life impairs adherens junctions and promotes tumorigenesis.
abstract: Serine palmitoyltransferase is the key enzyme in sphingolipid biosynthesis. Mice lacking serine palmitoyltransferase are embryonic lethal. We prepared liver-specific mice deficient in the serine palmitoyltransferase long chain base subunit 2 gene using an albumin-cyclization recombination approach and found that the deficient mice have severe jaundice. Moreover, the deficiency impairs hepatocyte polarity, attenuates liver regeneration after hepatectomy, and promotes tumorigenesis. Importantly, we show that the deficiency significantly reduces sphingomyelin but not other sphingolipids in hepatocyte plasma membrane; greatly reduces cadherin, the major protein in adherens junctions, on the membrane; and greatly induces cadherin phosphorylation, an indication of its degradation. The deficiency affects cellular distribution of β-catenin, the central component of the canonical Wnt pathway. Furthermore, such a defect can be partially corrected by sphingomyelin supplementation in vivo and in vitro.
  
  
  
  The plasma membrane sphingomyelin level is one of the key factors in regulating hepatocyte polarity and tumorigenesis. (Hepatology 2016;64:2089-2102).
authors.affiliation: Department of Cell Biology, Department of Surgery, and Department of Pathology, SUNY Downstate Medical Center.|Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, Brooklyn, NY.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Department of Surgery, and Department of Pathology, SUNY Downstate Medical Center.
authors.forename: Inamul
authors.initials: I
authors.lastname: Kabir
authors.affiliation: Department of Cell Biology, Department of Surgery, and Department of Pathology, SUNY Downstate Medical Center.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Nanjing Medical University, Nanjing, China.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Cell Biology, Department of Surgery, and Department of Pathology, SUNY Downstate Medical Center.
authors.forename: Jenny
authors.initials: J
authors.lastname: Libien
authors.affiliation: Department of Cell Biology, Department of Surgery, and Department of Pathology, SUNY Downstate Medical Center.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Cell Biology, Department of Surgery, and Department of Pathology, SUNY Downstate Medical Center.
authors.forename: Albert
authors.initials: A
authors.lastname: Stanek
authors.affiliation: Department of Cell Biology, Department of Surgery, and Department of Pathology, SUNY Downstate Medical Center.
authors.forename: Peiqi
authors.initials: P
authors.lastname: Ou
authors.affiliation: Department of Cell Biology, Department of Surgery, and Department of Pathology, SUNY Downstate Medical Center.
authors.forename: Kailyn R
authors.initials: KR
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Department of Surgery, and Department of Pathology, SUNY Downstate Medical Center.
authors.forename: Shane
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN.
authors.forename: Hai H
authors.initials: HH
authors.lastname: Bui
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN.
authors.forename: Ming-Shang
authors.initials: MS
authors.lastname: Kuo
authors.affiliation: Department of Life Science, Gachon University, Sungnam, South Korea.
authors.forename: Tae-Sik
authors.initials: TS
authors.lastname: Park
authors.affiliation: Department of Medicine, Columbia University, New York, NY.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Medicine, Columbia University, New York, NY.
authors.forename: Tilla S
authors.initials: TS
authors.lastname: Worgall
authors.affiliation: Department of Cell Biology, Department of Surgery, and Department of Pathology, SUNY Downstate Medical Center.
authors.forename: Chongmin
authors.initials: C
authors.lastname: Huan
authors.affiliation: Department of Cell Biology, Department of Surgery, and Department of Pathology, SUNY Downstate Medical Center.|Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, Brooklyn, NY.
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Jiang
mesh_terms: D022005:Adherens Junctions / Q000502:physiology*; D000367:Age Factors; D000818:Animals; D063646:Carcinogenesis; D008099:Liver / Q000201:enzymology*; D051379:Mice; D051102:Serine C-Palmitoyltransferase / Q000172:deficiency*
chemical_list: D051102:Serine C-Palmitoyltransferase