Transglutaminase 2 Regulates Self-renewal and Stem Cell Marker of Human Colorectal Cancer Stem Cells

Abstract

Background/aim: The aim of this study was to investigate the role of transglutaminase 2 (TGM2) in colorectal cancer stem cells (CCSCs).

Materials and methods: We used the TU12 cell line possessing CD133-expressing CCSCs. After isolating CD133 (-) and CD133 (+) CCSCs, we overexpressed and knocked-down TGM2 to investigate its role in human CCSCs.

Results: The expression level of TGM2 was 25-fold higher in tumorigenic cells than non-tumorigenic cells. We found that knockdown of TGM2 by specific RNA interference markedly inhibited cell growth and caused down-regulation of the stemness markers, CD133, SOX2, and β-catenin. We further demonstrated that knockdown of TGM2 inhibited cell metastatic abilities by down-regulating N-cadherin and vimentin and up-regulating E-cadherin. These findings revealed that TGM2 expression is markedly increased in human colorectal cancer and that down-regulation of TGM2 in tumors may serve as a treatment for colorectal cancer patients. Therefore, this study indicate that TGM2 affects the metastatic potential and stemness of CCSCs by regulating EMT- and stemness-related proteins.

Conclusion: The metastatic potential of CSCs arises from highly expressed TGM2.

Keywords: CCSC; EMT; TGM2; stemness.