Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle-upon-Tyne NE1 3BZ, UK.
Northern Institute for Cancer Research, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK.
Cancer Treat Rev. 2014 Apr;40(3):341-8. doi: 10.1016/j.ctrv.2013.09.008. Epub 2013 Sep 15.
There is increasing interest in cancer stem cells (CSCs) and their role in cancer progression. Recently, CSCs have been identified in brain, skin, and intestinal tumors and it has been suggested that these CSCs are responsible for tumor growth and metastasis. In breast cancer fatality is often due to the development of metastatic disease (MBC). Almost 30% of early breast cancer patients eventually develop MBC and in 90% of these multi-drug resistance (MDR) occurs. This could be attributed to the presence of breast cancer stem cells (BCSCs). Epithelial-to-mesenchymal transition (EMT) is a process known to contribute to metastasis in cancer and it is mainly characterized by loss of E-cadherin expression. The TGF-β signaling pathway has an established role in promoting EMT by down-regulating E-cadherin via a number of transcription factors, such as Twist, Snail and Slug. EMT has also been reported to produce cells with stem cell-like properties. Definition of the exact molecular mechanisms that are involved in the generation of stem cells through EMT could lead to the identification of new potential therapeutic targets and enable the development of more efficient strategies for particular patient groups. In this review we discuss what is known about the relationship between EMT, BCSCs and MDR.
人们对癌症干细胞（CSC）及其在癌症进展中的作用越来越感兴趣。最近，已经在脑、皮肤和肠道肿瘤中鉴定出了 CSC，并有人提出这些 CSC 负责肿瘤的生长和转移。在乳腺癌中，死亡率通常是由于转移性疾病（MBC）的发展。近 30%的早期乳腺癌患者最终会发展为 MBC，其中 90%会发生多药耐药（MDR）。这可能归因于乳腺癌干细胞（BCSC）的存在。上皮-间充质转化（EMT）是一种已知的促进癌症转移的过程，其主要特征是 E-钙粘蛋白表达的丧失。TGF-β 信号通路通过许多转录因子（如 Twist、Snail 和 Slug）下调 E-钙粘蛋白，在促进 EMT 方面发挥着既定作用。EMT 也被报道会产生具有干细胞样特性的细胞。明确参与 EMT 产生干细胞的具体分子机制，可以为确定新的潜在治疗靶点提供依据，并为特定患者群体开发更有效的策略。在这篇综述中，我们讨论了 EMT、BCSC 和 MDR 之间的关系。
