The role of tissue transglutaminase (TG2) in regulating the tumour progression of the mouse colon carcinoma CT26

Research output: Contribution to journalArticle

Abstract

The multifunctional enzyme tissue transglutaminase (TG2) is reported to both mediate and inhibit tumour progression. To elucidate these different roles of TG2, we established a series of stable-transfected mouse colon carcinoma CT26 cells expressing a catalytically active (wild type) and a transamidating-inactive TG2 (Cys277Ser) mutant. Comparison of the TG2-transfected cells with the empty vector control indicated no differences in cell proliferation, apoptosis and susceptibility to doxorubicin, which correlated with no detectable changes in the activation of the transcription factor NF-?B. TG2-transfected cells showed increased expression of integrin ß3, and were more adherent and less migratory on fibronectin than control cells. Direct interaction of TG2 with ß3 integrins was demonstrated by immunoprecipitation, suggesting that TG2 acts as a coreceptor for fibronectin with ß3 integrins. All cells expressed the same level of TGFß receptors I and II, but only cells transfected with active TG2 had increased levels of TGFß1 and matrix-deposited fibronectin, which could be inhibited by TG2 site-directed inhibitors. Moreover, only cells transfected with active TG2 were capable of inhibiting tumour growth when compared to the empty vector controls. We conclude that in this colon carcinoma model increased levels of active TG2 are unfavourable to tumour growth due to their role in activation of TGFß1 and increased matrix deposition, which in turn favours increased cell adhesion and a lowered migratory and invasive behaviour.
LanguageEnglish
Pages909-921
Number of pages13
JournalAmino Acids
Volume41
Issue number4
Early online date3 Nov 2010
DOIs
Publication statusPublished - Oct 2011

Fingerprint

Fibronectins
Integrins
Tumors
Colon
Carcinoma
Chemical activation
Multifunctional Enzymes
Neoplasms
Cell adhesion
Cell proliferation
Doxorubicin
Transcription Factors
Cells
Apoptosis
Growth
transglutaminase 2
Immunoprecipitation
Cell Adhesion
Cell Proliferation

Keywords

  • animals
  • CD29 antigens
  • apoptosis
  • cell adhesion
  • tumor cell line
  • cell movement
  • cell proliferation
  • Colonic Neoplasms
  • Doxorubicin
  • extracellular matrix
  • female
  • fibronectins
  • GTP-binding proteins
  • integrin beta chains
  • integrin beta3
  • mice
  • inbred BALB C mice
  • NF-kappa B
  • syndecan-4
  • transforming growth factor beta1
  • transglutaminases

Cite this

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title = "The role of tissue transglutaminase (TG2) in regulating the tumour progression of the mouse colon carcinoma CT26",
abstract = "The multifunctional enzyme tissue transglutaminase (TG2) is reported to both mediate and inhibit tumour progression. To elucidate these different roles of TG2, we established a series of stable-transfected mouse colon carcinoma CT26 cells expressing a catalytically active (wild type) and a transamidating-inactive TG2 (Cys277Ser) mutant. Comparison of the TG2-transfected cells with the empty vector control indicated no differences in cell proliferation, apoptosis and susceptibility to doxorubicin, which correlated with no detectable changes in the activation of the transcription factor NF-?B. TG2-transfected cells showed increased expression of integrin {\ss}3, and were more adherent and less migratory on fibronectin than control cells. Direct interaction of TG2 with {\ss}3 integrins was demonstrated by immunoprecipitation, suggesting that TG2 acts as a coreceptor for fibronectin with {\ss}3 integrins. All cells expressed the same level of TGF{\ss} receptors I and II, but only cells transfected with active TG2 had increased levels of TGF{\ss}1 and matrix-deposited fibronectin, which could be inhibited by TG2 site-directed inhibitors. Moreover, only cells transfected with active TG2 were capable of inhibiting tumour growth when compared to the empty vector controls. We conclude that in this colon carcinoma model increased levels of active TG2 are unfavourable to tumour growth due to their role in activation of TGF{\ss}1 and increased matrix deposition, which in turn favours increased cell adhesion and a lowered migratory and invasive behaviour.",
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The role of tissue transglutaminase (TG2) in regulating the tumour progression of the mouse colon carcinoma CT26. / Kotsakis, Panayiotis; Wang, Zhuo; Collighan, Russell John; Griffin, Martin.

In: Amino Acids, Vol. 41, No. 4, 10.2011, p. 909-921.

Research output: Contribution to journalArticle

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