Zheng Xiaobo, Dai Fuzhen, Feng Lei, Zou Hong, Feng Li, Xu Mingqing
Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.
Department of General Surgery, The First People's Hospital of Longquanyi District, Chengdu, China.
Front Oncol. 2021 Apr 21;11:617597. doi: 10.3389/fonc.2021.617597. eCollection 2021.
The epithelial-mesenchymal transition (EMT) is closely associated with the acquisition of aggressive traits by carcinoma cells and is considered responsible for metastasis, relapse, and chemoresistance. Molecular links between the EMT and cancer stem cells (CSCs) have indicated that EMT processes play important roles in the expression of CSC-like properties. It is generally thought that EMT-related transcription factors (EMT-TFs) need to be downregulated to confer an epithelial phenotype to mesenchymal cells and increase cell proliferation, thereby promoting metastasis formation. However, the genetic and epigenetic mechanisms that regulate EMT and CSC activation are contradictory. Emerging evidence suggests that EMT need not be a binary model and instead a hybrid epithelial/mesenchymal state. This dynamic process correlates with epithelial-mesenchymal plasticity, which indicates a contradictory role of EMT during cancer progression. Recent studies have linked the epithelial-mesenchymal plasticity and stem cell-like traits, providing new insights into the conflicting relationship between EMT and CSCs. In this review, we examine the current knowledge about the interplay between epithelial-mesenchymal plasticity and CSCs in cancer biology and evaluate the controversies and future perspectives. Understanding the biology of epithelial-mesenchymal plasticity and CSCs and their implications in therapeutic treatment may provide new opportunities for targeted intervention.
上皮-间质转化(EMT)与癌细胞侵袭性特征的获得密切相关,被认为是转移、复发和化疗耐药的原因。EMT与癌症干细胞(CSCs)之间的分子联系表明,EMT过程在CSC样特性的表达中起重要作用。一般认为,需要下调EMT相关转录因子(EMT-TFs),以使间充质细胞获得上皮表型并增加细胞增殖,从而促进转移灶形成。然而,调节EMT和CSC激活的遗传和表观遗传机制相互矛盾。新出现的证据表明,EMT不一定是二元模型,而是一种混合的上皮/间充质状态。这一动态过程与上皮-间质可塑性相关,这表明EMT在癌症进展过程中具有矛盾的作用。最近的研究将上皮-间质可塑性与干细胞样特征联系起来,为EMT和CSCs之间的矛盾关系提供了新的见解。在这篇综述中,我们研究了癌症生物学中关于上皮-间质可塑性与CSCs之间相互作用的现有知识,并评估了相关争议和未来展望。了解上皮-间质可塑性和CSCs的生物学特性及其在治疗中的意义,可能为靶向干预提供新的机会。