title: The complex role of transglutaminase 2 in glioblastoma proliferation.
abstract: BACKGROUND
  Glioblastomas (GBMs) are a heterogeneous group of primary brain tumors. These tumors are resistant to therapeutic interventions and invariably recur after surgical resection. The multifunctional protein transglutaminase 2 (TG2) has been shown to promote cell survival in a number of different tumors. There is also evidence that TG2 may be a pro-survival factor in GBMs. However, the roles that TG2 plays in facilitating GBM survival and proliferation have not yet been clearly delineated .
  
  
  METHODS
  The functions of TG2 are often cell- and context-specific. Therefore, in this study we examined the ability of TG2 to facilitate GBM proliferation using colony formation assays and 5-ethynyl-2'-deoxyuridine (EdU) incorporation in several different GBM cell lines as well as neurospheres derived from patient tumors representing the 3 major subtypes of GBM tumors (mesenchymal, proneural, and classical) and maintained in the absence of serum. TG2 knockdown or selective TG2 inhibitors were used to modulate TG2 expression and activity.
  
  
  RESULTS
  We show that TG2 plays differential roles in the proliferative process depending on the cell type. In most, but not all, GBM models TG2 plays a crucial role in the proliferative process, and some but not all TG2 inhibitors were highly effective at reducing proliferation in a large subset of the GBM models.
  
  
  CONCLUSIONS
  Our results show that TG2 plays an important-but notoriously context-specific-role in GBM cell biology. Nonetheless, as future studies unravel the genetic "fingerprints" that make TG2 inhibitors effective, this information could be exploited to develop TG2 inhibitors into personalized GBM therapies.
authors: Department of Anesthesiology, University of Rochester, Rochester, New York; Department of Pharmacology and Physiology, University of Rochester, Rochester, New York; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
authors: Soner
authors: S
authors: Gundemir
authors: Department of Anesthesiology, University of Rochester, Rochester, New York; Department of Pharmacology and Physiology, University of Rochester, Rochester, New York; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
authors: Alina
authors: A
authors: Monteagudo
authors: Department of Anesthesiology, University of Rochester, Rochester, New York; Department of Pharmacology and Physiology, University of Rochester, Rochester, New York; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
authors: Abdullah
authors: A
authors: Akbar
authors: Department of Anesthesiology, University of Rochester, Rochester, New York; Department of Pharmacology and Physiology, University of Rochester, Rochester, New York; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
authors: Jeffrey W
authors: JW
authors: Keillor
authors: Department of Anesthesiology, University of Rochester, Rochester, New York; Department of Pharmacology and Physiology, University of Rochester, Rochester, New York; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
authors: Gail V W
authors: GVW
authors: Johnson
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine
keywords: glioblastoma; neurospheres; proliferation; transglutaminase 2; transglutaminase 2 inhibitors