title: Zeb1 affects epithelial cell adhesion by diverting glycosphingolipid metabolism.
abstract: This study proposes that the transcription factor Zeb1 modulates epithelial cell adhesion by diverting glycosphingolipid metabolism. Zeb1 promotes expression of a-series glycosphingolipids via regulating expression of GM3 synthase (St3gal5), which mechanistically involves Zeb1 binding to the St3gal5 promoter as well as suppressing microRNA-mediated repression of St3gal5. Functionally, the repression of St3gal5 suffices to elevate intercellular adhesion and expression of distinct junction-associated proteins, reminiscent of knockdown of Zeb1. Conversely, overexpressing St3gal5 sensitizes cells towards TGF-β1-induced disruption of cell-cell interaction and partially antagonizes elevation of intercellular adhesion imposed by Zeb1 knockdown. These results highlight a direct connection of glycosphingolipid metabolism and epithelial cell adhesion via Zeb1.
authors: Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Daniel
authors: D
authors: Mathow
authors: Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Federica
authors: F
authors: Chessa
authors: Department of Cellular and Molecular Pathology, Lipid Pathobiochemistry Group German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Mariona
authors: M
authors: Rabionet
authors: Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Sylvia
authors: S
authors: Kaden
authors: Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Richard
authors: R
authors: Jennemann
authors: Department of Cellular and Molecular Pathology, Lipid Pathobiochemistry Group German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Roger
authors: R
authors: Sandhoff
authors: Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), Heidelberg, Germany h.-j.groene@dkfz-heidelberg.de alexander.feuerborn@path.ox.ac.uk.
authors: Hermann-Josef
authors: HJ
authors: Gröne
authors: Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), Heidelberg, Germany Sir William Dunn School of Pathology, University of Oxford, Oxford, UK h.-j.groene@dkfz-heidelberg.de alexander.feuerborn@path.ox.ac.uk.
authors: Alexander
authors: A
authors: Feuerborn
mesh_terms: D000818:Animals; D001399:Azure Stains; D002448:Cell Adhesion / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006028:Glycosphingolipids / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D012799:Sialyltransferases / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D001399:Azure Stains; D006028:Glycosphingolipids; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1; D012799:Sialyltransferases; C021343:haematoside synthetase
keywords: EMT; TGF‐β1; Zeb1; adhesion; glycosphingolipids
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