Subhadarshini Seemadri, Markus Joel, Sahoo Sarthak, Jolly Mohit Kumar
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India.
ACS Omega. 2023 Mar 22;8(13):11665-11673. doi: 10.1021/acsomega.2c07989. eCollection 2023 Apr 4.
Epithelial-mesenchymal plasticity (EMP) is a key driver of cancer metastasis and therapeutic resistance, through which cancer cells can reversibly and dynamically alter their molecular and functional traits along the epithelial-mesenchymal spectrum. While cells in the epithelial phenotype are usually tightly adherent, less metastatic, and drug-sensitive, those in the hybrid epithelial/mesenchymal and/or mesenchymal state are more invasive, migratory, drug-resistant, and immune-evasive. Single-cell studies have emerged as a powerful tool in gaining new insights into the dynamics of EMP across various cancer types. Here, we review many recent studies that employ single-cell analysis techniques to better understand the dynamics of EMP in cancer both in vitro and in vivo. These single-cell studies have underlined the plurality of trajectories cells can traverse during EMP and the consequent heterogeneity of hybrid epithelial/mesenchymal phenotypes seen at both preclinical and clinical levels. They also demonstrate how diverse EMP trajectories may exhibit hysteretic behavior and how the rate of such cell-state transitions depends on the genetic/epigenetic background of recipient cells, as well as the dose and/or duration of EMP-inducing growth factors. Finally, we discuss the relationship between EMP and patient survival across many cancer types. We also present a next set of questions related to EMP that could benefit much from single-cell observations and pave the way to better tackle phenotypic switching and heterogeneity in clinic.
上皮-间质可塑性（EMP）是癌症转移和治疗抵抗的关键驱动因素，通过这一过程癌细胞能够沿着上皮-间质谱系可逆且动态地改变其分子和功能特性。上皮表型的细胞通常紧密黏附，转移能力较低且对药物敏感，而处于上皮/间质混合状态和/或间质状态的细胞则更具侵袭性、迁移性、耐药性且能逃避免疫监视。单细胞研究已成为一种强大的工具，有助于深入了解各种癌症类型中EMP的动态变化。在此，我们综述了许多近期的研究，这些研究采用单细胞分析技术，以便更好地理解癌症在体外和体内EMP的动态变化。这些单细胞研究强调了细胞在EMP过程中可以经历的多种轨迹，以及在临床前和临床水平所见的上皮/间质混合表型的异质性。它们还展示了不同的EMP轨迹如何可能表现出滞后行为，以及这种细胞状态转变的速率如何取决于受体细胞的遗传/表观遗传背景，以及EMP诱导生长因子的剂量和/或持续时间。最后，我们讨论了EMP与多种癌症类型患者生存之间的关系。我们还提出了与EMP相关的下一组问题，这些问题可能会从单细胞观察中受益匪浅，并为在临床上更好地应对表型转换和异质性铺平道路。
