Garg Minal
Department of Biochemistry, University of Lucknow, Lucknow, 226007, India.
Cancer Metastasis Rev. 2015 Dec;34(4):691-701. doi: 10.1007/s10555-015-9589-6.
Urothelial carcinoma is a highly heterogeneous disease that develops along two distinct biological tracks as evident by candidate gene analysis and genome-wide screening and therefore, offers different challenges for clinical management. Tumors representing the truly distinct molecular entities express molecular markers characteristic of a developmental process and a major mechanism of cancer metastasis, known as epithelial-to-mesenchymal transition (EMT). Recently identified subset of cells known as urothelial cancer stem cells (UroCSCs) in urothelial cell carcinoma (UCC) have self-renewal properties, ability to generate cellular tumor heterogeneity via differentiation and are ultimately responsible for tumor growth and viability. In this review paper, PubMed and Google Scholar electronic databases were searched for original research papers and review articles to extract relevant information on the molecular mechanisms delineating the relationship between EMT and cancer stemness and their clinical implications for different subsets of urothelial cell carcinomas. Experimental and clinical studies over the past few years in bladder cancer cell lines and tumor tissues of different cancer subtypes provide evidences and new insights for mechanistic complexity for induction of EMT, tumorigenicity, and cancer stemness in malignant transformation of urothelial cell carcinomas. Differentiation and elimination therapies targeting EMT-cancer stemness pathway have been proposed as cynosure in the molecular biology of urothelial cell carcinomas and could prove to be clinically beneficial in an ability to reverse the EMT phenotype of tumor cells, suppress the properties of UroCSCs, inhibit bladder cancer progression and tumor relapse, and provide rationale in the treatment and clinical management of urothelial cancer.
尿路上皮癌是一种高度异质性疾病，通过候选基因分析和全基因组筛查可明显看出其沿着两条不同的生物学轨迹发展，因此给临床管理带来了不同挑战。代表真正不同分子实体的肿瘤表达出发育过程和癌症转移主要机制（即上皮-间质转化，EMT）所特有的分子标志物。最近在尿路上皮细胞癌（UCC）中发现的被称为尿路上皮癌干细胞（UroCSCs）的细胞亚群具有自我更新特性，能够通过分化产生细胞肿瘤异质性，最终对肿瘤生长和存活负责。在这篇综述文章中，检索了PubMed和谷歌学术电子数据库中的原始研究论文和综述文章，以提取有关描述EMT与癌症干性之间关系的分子机制及其对不同尿路上皮细胞癌亚群临床意义的相关信息。过去几年在不同癌症亚型的膀胱癌细胞系和肿瘤组织中进行的实验和临床研究，为尿路上皮细胞癌恶性转化过程中EMT诱导、致瘤性和癌症干性的机制复杂性提供了证据和新见解。针对EMT-癌症干性途径的分化和消除疗法已被提议作为尿路上皮细胞癌分子生物学的焦点，并且在逆转肿瘤细胞的EMT表型、抑制UroCSCs特性、抑制膀胱癌进展和肿瘤复发的能力方面可能具有临床益处，为尿路上皮癌的治疗和临床管理提供理论依据。
