Abell Amy N, Johnson Gary L
Departments of Biological Sciences and Biomedical Engineering, University of Memphis, Memphis, TN 38152, USA.
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7365, USA.
Curr Pathobiol Rep. 2014 Mar;2(1):21-26. doi: 10.1007/s40139-013-0034-7.
The epithelial to mesenchymal transition (EMT) generates tumor cells having stem cell characteristics with phenotypes similar to cancer stem cells (CSCs). Evidence suggests CSCs are in an intermediate state of EMT expressing reduced levels of E-cadherin and exhibiting mesenchymal features including invasiveness associated with metastasis. These findings suggest mechanisms regulating EMT and stemness are closely integrated. Recent reports from multiple laboratories have identified novel mechanisms regulating EMT and stemness involving epigenetics, microenvironment, and dedifferentiation. Circulating tumor cells (CTCs) have also been shown to exhibit features of EMT, but it is unclear what fraction has CSCs properties. EMT characteristics of both CSCs and CTCs are associated with resistance to current clinical treatments, indicating therapies targeting the CSC in addition to the more differentiated tumor cells are required for durable responses. Thus, EMT characteristics of CTCs may prove useful biomarkers for effective therapies for many cancers.
上皮-间质转化(EMT)产生具有干细胞特征的肿瘤细胞,其表型与癌症干细胞(CSC)相似。有证据表明,CSC处于EMT的中间状态,E-钙黏蛋白表达水平降低,并表现出包括与转移相关的侵袭性在内的间质特征。这些发现表明,调节EMT和干性的机制紧密相连。多个实验室最近的报告已经确定了调节EMT和干性的新机制,涉及表观遗传学、微环境和去分化。循环肿瘤细胞(CTC)也已被证明具有EMT特征,但尚不清楚具有CSC特性的CTC比例是多少。CSC和CTC的EMT特征都与对当前临床治疗的抗性相关,这表明除了更分化的肿瘤细胞外,还需要针对CSC的疗法才能获得持久反应。因此,CTC的EMT特征可能成为许多癌症有效治疗的有用生物标志物。