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Research Article Open access CC BY 4.0

The Role of Transglutaminase 2 (TG2) in Definition of Cancer Hallmarks

Odii Benedict Onyekachi, U. Lawani Ebidor, Omabe Maxwell

Journal of Advances in Medicine and Medical Research · pp. 297–311 · Published 15 Dec 2014

10.9734/BJMMR/2015/13919

Abstract

Over the past three decades, TGM2, a stress-responsive gene encoding transglutaminase 2 (TG2) has been identified as one of the several genes that may be involved in carcinogenesis and cancer physiology. TG2 is a pleiotropic calcium-dependent enzyme belonging to the transglutaminase family of enzymes, which post-translationally modify glutaminyl and lysyl side chains on the surface of both in vivo and in vitro substrate proteins. Unlike other members of the transglutaminase family, TG2 has additional Ca2+-independent enzymatic and non-enzymatic activities, which have been directly or indirectly implicated in diverse cellular physiological events, including cell growth and differentiation, cell adhesion and morphology, extracellular matrix stabilization, wound healing, cellular development, receptor-mediated endocytosis, apoptosis, and disease pathology. TG2 has specialized biochemical, structural and functional elements, wide tissue distribution and sub-cellular localisation, as well as broad substrate specificity. These specialised features of TG2 account for its multiple patho-physiological functionalities. Considering the multiplicity of TG2 functions and its importance in disease pathology, including cancer; we have reviewed herein, the importance of TG2 in the definition of the hallmark capabilities of cancer cells. This was done with the view to deepen our understanding of the role of TG2 in carcinogenesis and recapitulating its potential as a therapeutic target for cancer treatment.

Transglutaminase 2 cancer drug resistance metastasis apoptosis

References (78)

  1. 1 The Hallmarks of Cancer [DOI]
  2. 2 Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis [DOI]
  3. 3 The Clonal Evolution of Tumor Cell Populations [DOI]
  4. 4 The retinoblastoma protein and cell cycle control [DOI]
  5. 5 Transglutaminases: crosslinking enzymes with pleiotropic functions [DOI]
  6. 6 Intrinsic tumour suppression [DOI]
  7. 7 Transglutaminases: Nature’s biological glues [DOI]
  8. 8 Cellular mechanisms of tumour suppression by the retinoblastoma gene [DOI]
  9. 9 G h : a GTP-Binding Protein with Transglutaminase Activity and Receptor Signaling Function [DOI]
  10. 10 Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin [DOI]
  11. 11 The ins and outs of fibronectin matrix assembly [DOI]
  12. 12 Cyclins and cdks in development and cancer: a perspective [DOI]
  13. 13 Protein Crosslinking in Assembly and Remodelling of Extracellular Matrices: The Role of Transglutaminases [DOI]
  14. 14 Transglutaminase 2 inhibitor, KCC009, disrupts fibronectin assembly in the extracellular matrix and sensitizes orthotopic glioblastomas to chemotherapy [DOI]
  15. 15 Transglutaminase 2: A multi-tasking protein in the complex circuitry of inflammation and cancer [DOI]
  16. 16 Matrix-dependent Proteolysis of Surface Transglutaminase by Membrane-type Metalloproteinase Regulates Cancer Cell Adhesion and Locomotion [DOI]
  17. 17 Mortality and immortality at the cellular level. A review.
  18. 18 Distinct Nuclear Localization and Activity of Tissue Transglutaminase [DOI]
  19. 19 A Novel RGD-independent Cell Adhesion Pathway Mediated by Fibronectin-bound Tissue Transglutaminase Rescues Cells from Anoikis [DOI]
  20. 20 Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth [DOI]
  21. 21 The incorporation of fibrinogen into extracellular matrix is dependent on active assembly of a fibronectin matrix [DOI]
  22. 22 Tissue transglutaminase (TG2) - a wound response enzyme [DOI]
  23. 23 Intracellular Localization and Activity State of Tissue Transglutaminase Differentially Impacts Cell Death [DOI]
  24. 24 Tissue Transglutaminase Protects against Apoptosis by Modifying the Tumor Suppressor Protein p110 Rb [DOI]
  25. 25 High levels of transglutaminase expression in doxorubicin‐resistant human breast carcinoma cells [DOI]
  26. 26 Tissue transglutaminase-mediated chemoresistance in cancer cells [DOI]
  27. 27 Transglutaminase 2 as a cisplatin resistance marker in non-small cell lung cancer [DOI]
  28. 28 Therapeutic Significance of Elevated Tissue Transglutaminase Expression in Pancreatic Cancer [DOI]
  29. 29 Identification of a Novel Recognition Sequence for Fibronectin within the NH2-terminal β-Sandwich Domain of Tissue Transglutaminase [DOI]
  30. 30 Complexation of fibronectin with tissue transglutaminase [DOI]
  31. 31 Interaction of tissue transglutaminase with nuclear transport protein importin‐α3 [DOI]
  32. 32 Tissue transglutaminase: from biological glue to cell survival cues [DOI]
  33. 33 New insights into the functions and localization of nuclear transglutaminase 2 [DOI]
  34. 34 Evidence That Aberrant Expression of Tissue Transglutaminase Promotes Stem Cell Characteristics in Mammary Epithelial Cells [DOI]
  35. 35 Transglutaminase 2 Overexpression in Tumor Stroma Identifies Invasive Ductal Carcinomas of Breast at High Risk of Recurrence [DOI]
  36. 36 Regulated Expression of Tissue Transglutaminase in Swiss 3T3 Fibroblasts: Effects on the Processing of Fibronectin, Cell Attachment, and Cell Death [DOI]
  37. 37 Absence of oats toxicity in adult coeliac disease: Table 1 [DOI]
  38. 38 Cell Surface Localization of Tissue Transglutaminase Is Dependent on a Fibronectin-binding Site in Its N-terminal β-Sandwich Domain [DOI]
  39. 39 Interaction Site of GTP Binding Gh (Transglutaminase II) with Phospholipase C [DOI]
  40. 40 Transglutaminase-mediated processing of fibronectin by endothelial cell monolayers [DOI]
  41. 41 GTP Binding and Signaling by Gh/Transglutaminase II Involves Distinct Residues in a Unique GTP-binding Pocket [DOI]
  42. 42 Identification and biochemical characterization of an 80 kilodalton GTP-binding/transglutaminase from rabbit liver nuclei [DOI]
  43. 43 Affinity of human erythrocyte transglutaminase for a 42-kDa gelatin-binding fragment of human plasma fibronectin. [DOI]
  44. 44 Ligand-Induced Conformational Changes in Tissue Transglutaminase: Monte Carlo Analysis of Small-Angle Scattering Data [DOI]
  45. 45 Depletion of nucleophosmin via transglutaminase 2 cross-linking increases drug resistance in cancer cells [DOI]
  46. 46 Tissue Transglutaminase at Embryo-Maternal Interface [DOI]
  47. 47 Transglutaminase 2 expression in acute myeloid leukemia: Association with adhesion molecule expression and leukemic blast motility [DOI]
  48. 48 Survival pathways meet their end [DOI]
  49. 49 Conformational Changes in the Nucleosome Followed by the Selective Accessibility of Histone Glutamines in the Transglutaminase Reaction: Effects of Ionic Strength [DOI]
  50. 50 COMMENTARY: p53 Tumor suppressor gene: from the basic research laboratory to the clinic—an abridged historical perspective [DOI]
  51. 51 Hallmarks of Cancer: The Next Generation [DOI]
  52. 52 The Bcl-2 apoptotic switch in cancer development and therapy [DOI]
  53. 53 New York, USA
  54. 54 Fibronectin Polymerization Regulates the Composition and Stability of Extracellular Matrix Fibrils and Cell-Matrix Adhesions [DOI]
  55. 55 The angiogenic switch in carcinogenesis [DOI]
  56. 56 Transglutaminase 2: an enigmatic enzyme with diverse functions [DOI]
  57. 57 Roles for Growth Factors in Cancer Progression [DOI]
  58. 58 Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies.
  59. 59 Oats induced villous atrophy in coeliac disease [DOI]
  60. 60 Prognostic Significance of Tissue Transglutaminase in Drug Resistant and Metastatic Breast Cancer [DOI]
  61. 61 The role of tissue transglutaminase in cell-matrix interactions [DOI]
  62. 62 Evidence that GTP-binding domain but not catalytic domain of transglutaminase 2 is essential for epithelial-to-mesenchymal transition in mammary epithelial cells [DOI]
  63. 63 Expression of tissue transglutaminase in Balb-C 3T3 fibroblasts: effects on cellular morphology and adhesion. [DOI]
  64. 64 Cell-surface transglutaminase promotes fibronectin assembly via interaction with the gelatin-binding domain of fibronectin [DOI]
  65. 65 Increased Expression of Tissue Transglutaminase in Pancreatic Ductal Adenocarcinoma and Its Implications in Drug Resistance and Metastasis [DOI]
  66. 66 Localization of cellular transglutaminase on the extracellular matrix after wounding: Characteristics of the matrix bound enzyme [DOI]
  67. 67 Enhanced Peritoneal Ovarian Tumor Dissemination by Tissue Transglutaminase [DOI]
  68. 68 Augmentation of Tissue Transglutaminase Expression and Activation by Epidermal Growth Factor Inhibit Doxorubicin-induced Apoptosis in Human Breast Cancer Cells [DOI]
  69. 69 Implications of tissue transglutaminase expression in malignant melanoma [DOI]
  70. 70 Identification of the Calcium Binding Site and a Novel Ytterbium Site in Blood Coagulation Factor XIII by X-ray Crystallography [DOI]
  71. 71 Tissue transglutaminase as a central mediator in inflammation-induced progression of breast cancer [DOI]
  72. 72 Crystal Structure of Red Sea Bream Transglutaminase [DOI]
  73. 73 Opposite Effects of Ca2+ and GTP Binding on Tissue Transglutaminase Tertiary Structure [DOI]
  74. 74 Tissue transglutaminase mediates the pro‐malignant effects of oncostatin M receptor over‐expression in cervical squamous cell carcinoma [DOI]
  75. 75 Biological Functionalities of Transglutaminase 2 and the Possibility of Its Compensation by Other Members of the Transglutaminase Family [DOI]
  76. 76 Conserved tryptophan in the core domain of transglutaminase is essential for catalytic activity [DOI]
  77. 77 Transglutaminase 2 Expression Predicts Progression Free Survival in Non-Small Cell Lung Cancer Patients Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor [DOI]
  78. 78 Multidrug-resistant MCF-7 breast cancer cells contain deficient intracellular calcium pools [DOI]

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