Tissue transglutaminase links TGF-β, epithelial to mesenchymal transition and a stem cell phenotype in ovarian cancer.

作者: L Cao , M Shao , J Schilder , T Guise , K S Mohammad

DOI: 10.1038/ONC.2011.429

关键词: Cancer researchOvarian cancerBiologyCD44MetastasisCD117Ovarian tumorEpithelial–mesenchymal transitionCell cultureCancer stem cell

摘要: Tissue transglutaminase (TG2), an enzyme involved in cell proliferation, differentiation and apoptosis is overexpressed ovarian carcinomas, where it modulates epithelial-to-mesenchymal transition (EMT) promotes metastasis. Its regulation cancer (OC) remains unexplored. Here, we show that transforming growth factor (TGF)-β, a cytokine tumor dissemination abundantly secreted the OC microenvironment induces TG2 expression enzymatic activity. This mediated at transcriptional level by SMADs TGF-β-activated kinase 1-mediated activation of nuclear factor-κB complex. TGF-β-stimulated cells aggregate as spheroids, which enable peritoneal dissemination. We TGF-β-induced regulates EMT, formation spheroids knock-down decreases number harboring stem phenotype (CD44+/CD117+). Furthermore, CD44+/CD117+ isolated from human tumors express high levels TG2. In summary, enhances metastasis inducing EMT phenotype.

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