Research Papers:

Tissue transglutaminase induces Epithelial-Mesenchymal-Transition and the acquisition of stem cell like characteristics in colorectal cancer cells

Oluseyi Ayinde, Zhuo Wang and Martin Griffin _

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Oncotarget. 2017; 8:20025-20041. https://doi.org/10.18632/oncotarget.15370

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Oluseyi Ayinde1, Zhuo Wang1, Martin Griffin1

1School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, United Kingdom

Correspondence to:

Martin Griffin, email: [email protected]

Zhuo Wang, email: [email protected]

Keywords: tissue transglutaminase, Epithelial-Mesenchymal Transition, cancer stem cells, colorectal cancer

Received: September 26, 2016    Accepted: January 07, 2017    Published: February 16, 2017


Human colon cancer cell lines (CRCs) RKO, SW480 and SW620 were investigated for TG2 involvement in tumour advancement and aggression. TG2 expression correlated with tumour advancement and expression of markers of epithelial-mesenchymal transition (EMT). The metastatic cell line SW620 showed high TG2 expression compared to the primary tumour cell lines SW480 and RKO and could form tumour spheroids under non- adherent conditions. TG2 manipulation in the CRCs by shRNA or TG2 transduction confirmed the relationship between TG2 and EMT. TGFβ1 expression in CRC cells, and its level in the cell medium and extracellular matrix was increased in primary tumour CRCs overexpressing TG2 and could regulate TG2 expression and EMT by both canonical (RKO) and non-canonical (RKO and SW480) signalling. TGFβ1 regulation was not observed in the metastatic SW620 cell line, but TG2 knockdown or inhibition in SW620 reversed EMT. In SW620, TG2 expression and EMT was associated with increased presence of nuclear β-catenin which could be mediated by association of TG2 with the Wnt signalling co-receptor LRP5. TG2 inhibition/knockdown increased interaction between β-catenin and ubiquitin shown by co-immunoprecipitation, suggesting that TG2 could be important in β-catenin regulation. β-Catenin and TG2 was also upregulated in SW620 spheroid cells enriched with cancer stem cell marker CD44 and TG2 inhibition/knockdown reduced the spheroid forming potential of SW620 cells. Our data suggests that TG2 could hold both prognostic and therapeutic significance in colon cancer.

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