Inhibition of hepatocellular carcinoma growth by blockade of glycosphingolipid synthesis

Oncotarget
Richard JennemannHermann-Josef Gröne

Abstract

Hepatocellular carcinoma (HCC) is one of the most frequent cancers. In vitro studies suggest that growth and response to therapy of human carcinomas may depend on glycosphingolipid (GSL) expression. Glucosylceramide synthase (GCS), encoded by the gene Ugcg, is the basic enzyme required for the synthesis of GSLs. Gene array analysis implied that Ugcg is significantly overexpressed in human HCC as compared to non-tumorous liver tissue. Therefore we have investigated whether tumor - genesis and - growth is altered in the absence of GSLs. An endogenous liver cancer model has been initiated by application of diethylnitrosamine in mice lacking Ugcg specifically in hepatocytes. We have now shown that hepatocellular tumor initiation and growth in mice is significantly inhibited by hepatic GSL deficiency in vivo. Neither the expression of cell cycle proteins, such as cyclins and pathways such as the MAP-kinase/Erk pathway nor the mTOR/Akt pathway as well as the number of liver infiltrating macrophages and T cells were essentially changed in tumors lacking GSLs. Significantly elevated bi-nucleation of atypical hepatocytes, a feature for impaired cytokinesis, was detected in tumors of mice lacking liver-specific GSLs. A reduction of proli...Continue Reading

References

Nov 1, 1991·Glycobiology·R L Schnaar
Jan 1, 1993·Virchows Archiv. B, Cell Pathology Including Molecular Pathology·B N KudryavtsevG I Stein
Mar 19, 1993·Science·L M ObeidY A Hannun
Jan 27, 1999·Biochemical and Biophysical Research Communications·S IchikawaY Hirabayashi
Oct 24, 2001·The Journal of Cell Biology·H SprongG van Meer
Nov 15, 2001·The Journal of Biological Chemistry·Seiichi TagamiYasuyuki Igarashi
Mar 11, 2003·The Journal of Biological Chemistry·Jacques-Emmanuel GuidottiChantal Desdouets
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Tadashi YamashitaRichard L Proia
May 29, 2003·Biochimie·S BirkléJ Aubry
Jul 24, 2004·Seminars in Cell & Developmental Biology·Timothy Hla
Jul 26, 2006·World Journal of Gastroenterology : WJG·Paula Jakszyn, Carlos-Alberto Gonzalez
Aug 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kazuya KabayamaJin-ichi Inokuchi
Sep 27, 2007·Journal of Cell Science·Germain Margall-DucosChantal Desdouets
Jan 4, 2008·Breast Cancer Research : BCR·Yuchao GuWengong Yu
Feb 20, 2009·Journal of Gastroenterology·Stephen Caldwell, Sang H Park
Apr 2, 2009·Biological Chemistry·Aurélie CazetPhilippe Delannoy
Jan 2, 2010·Science·Daniel Lingwood, Kai Simons
May 1, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Richard JennemannHermann-Josef Gröne
May 1, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Brad Q StarleyStephen A Harrison
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Roger A KroesJoseph R Moskal
Aug 7, 2010·Advances in Experimental Medicine and Biology·Guillaume Normand, Randall W King
May 17, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ünal CoskunKai Simons
Jun 2, 2011·Toxicologic Pathology·Masahiko KushidaJames E Klaunig
Jun 28, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wei-Ching HuangChiou-Feng Lin
Oct 18, 2011·Trends in Cell Biology·Michael MaceykaSarah Spiegel
Nov 1, 2011·Human Molecular Genetics·Richard JennemannRoger Sandhoff

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Citations

Dec 6, 2019·International Journal of Molecular Sciences·Miroslav MachalaJan Vondráček
Mar 10, 2020·Glycobiology·Richard JennemannHermann-Josef Gröne
Jul 24, 2020·Pharmacological Reports : PR·Tanweer HaiderVandana Soni
Jun 7, 2019·International Journal of Obesity : Journal of the International Association for the Study of Obesity·V DieterleV Nordström
Feb 15, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Christa Buechler, Charalampos Aslanidis
Apr 23, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zibo LiCaiyan Wang
Jun 4, 2021·Molecular Immunology·M L M JongsmaR M Spaapen
Sep 24, 2019·Current Medicinal Chemistry·Petra GrbčićMirela Sedić

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Datasets Mentioned

BETA
GSE64041
GM2

Methods Mentioned

BETA
xenograft
transfection
targeted mutation
FACS

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