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


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.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Aston University (General)
Uncontrolled 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,Biochemistry,Clinical Biochemistry,Organic Chemistry
Publication ISSN: 1438-2199
Last Modified: 22 Apr 2024 07:09
Date Deposited: 19 Aug 2019 08:53
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2011-10
Published Online Date: 2010-11-03
Authors: Kotsakis, Panayiotis
Wang, Zhuo (ORCID Profile 0000-0002-2212-8318)
Collighan, Russell John (ORCID Profile 0000-0003-0204-5125)
Griffin, Martin (ORCID Profile 0000-0003-3824-306X)



Version: Accepted Version

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