title: Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition.
abstract: Type II transglutaminase (TG2) is a multifunctional protein that has recently been implicated as having a role in ECS cell survival. In the present study we investigate the role of TG2 in regulating epithelial mesenchymal transition (EMT) in ECS cells. Our studies show that TG2 knockdown or treatment with TG2 inhibitor, results in a reduced EMT marker expression, and reduced cell migration and invasion. TG2 has several activities, but the most prominent are its transamidase and GTP binding activity. Analysis of a series of TG2 mutants reveals that TG2 GTP binding activity, but not the transamidase activity, is required for expression of EMT markers (Twist, Snail, Slug, vimentin, fibronectin, N-cadherin and HIF-1α), and increased ECS cell invasion and migration. This coupled with reduced expression of E-cadherin. Additional studies indicate that NFÏ°B signaling, which has been implicated as mediating TG2 impact on EMT in breast cancer cells, is not involved in TG2 regulation of EMT in skin cancer. These studies suggest that TG2 is required for maintenance of ECS cell EMT, invasion and migration, and suggests that inhibiting TG2 GTP binding/G-protein related activity may reduce skin cancer tumor survival.
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Fisher
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Adhikary
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Candace
authors.initials: C
authors.lastname: Kerr
authors.affiliation: Department of Chemistry, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Keillor
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Dermatology, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Reproductive Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Marlene and Stewart Greenebaum Cancer, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Eckert
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D019204:GTP-Binding Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015398:Signal Transduction; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: TG2; cancer stem cell; epidermal squamous cell carcinoma; epithelial mesenchymal transition; type II transglutaminase