作者: L Cao , M Shao , J Schilder , T Guise , K S Mohammad
DOI: 10.1038/ONC.2011.429
关键词: Cancer research 、 Ovarian cancer 、 Biology 、 CD44 、 Metastasis 、 CD117 、 Ovarian tumor 、 Epithelial–mesenchymal transition 、 Cell culture 、 Cancer 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.