上海市浦东新区迎春路2277号牌楼
Heterogeneity and plasticity of epithelial-mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms.
发表日期:2023 Feb 19
作者:
Dandan Li, Lingyun Xia, Pan Huang, Zidi Wang, Qiwei Guo, Congcong Huang, Weidong Leng, Shanshan Qin
来源:
CELL PROLIFERATION
摘要:
上皮-间充质转化(EMT)或间充质-上皮转化(MET)在癌症转移中具有关键作用。最近的研究,特别是基于单细胞测序的,揭示了EMT不是二进制过程,而是中间或部分EMT状态的异质性和动态性。多个EMT相关转录因子(EMT-TFs)介导的双负反馈回路已被鉴定。这些反馈回路在EMT驱动者和MET驱动者之间细致地调节细胞的EMT转化状态。本综述总结了不同EMT转换状态的一般特征、生物标志物和分子机制。我们还讨论了EMT转换状态在肿瘤转移中的直接和间接作用。更重要的是,本文提供了直接证据表明EMT的异质性与胃癌的恶劣预后密切相关。值得注意的是,我们提出了一个“跷跷板模型”,用以解释肿瘤细胞如何调控自身以保持特定的EMT转化状态,包括上皮状态、杂交/中间状态和间充质状态。此外,本文还对EMT信号的临床应用现状、局限性和未来展望进行了综述。
© 2023年作者。由北京干细胞与再生医学研究所和约翰威利有限公司出版的《细胞增殖》。
Epithelial-mesenchymal transition (EMT) or mesenchymal-epithelial transition (MET) plays critical roles in cancer metastasis. Recent studies, especially those based on single-cell sequencing, have revealed that EMT is not a binary process, but a heterogeneous and dynamic disposition with intermediary or partial EMT states. Multiple double-negative feedback loops involved by EMT-related transcription factors (EMT-TFs) have been identified. These feedback loops between EMT drivers and MET drivers finely regulate the EMT transition state of the cell. In this review, the general characteristics, biomarkers and molecular mechanisms of different EMT transition states were summarized. We additionally discussed the direct and indirect roles of EMT transition state in tumour metastasis. More importantly, this article provides direct evidence that the heterogeneity of EMT is closely related to the poor prognosis in gastric cancer. Notably, a seesaw model was proposed to explain how tumour cells regulate themselves to remain in specific EMT transition states, including epithelial state, hybrid/intermediate state and mesenchymal state. Additionally, this article also provides a review of the current status, limitations and future perspectives of EMT signalling in clinical applications.© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.