Hudson Institute of Medical Research, Clayton 3168, Australia.
Department of Molecular and Translational Sciences, Monash University, Clayton 3168, Australia.
Int J Mol Sci. 2024 Sep 30;25(19):10554. doi: 10.3390/ijms251910554.
Metastasis is the leading cause of cancer-related mortality; however, a complete understanding of the molecular programs driving the metastatic cascade is lacking. Metastasis is dependent on collective invasion-a developmental process exploited by many epithelial cancers to establish secondary tumours and promote widespread disease. The key drivers of collective invasion are "Leader Cells", a functionally distinct subpopulation of cells that direct migration, cellular contractility, and lead trailing or follower cells. While a significant body of research has focused on leader cell biology in the traditional context of collective invasion, the influence of metastasis-promoting leader cells is an emerging area of study. This review provides insights into the expanded role of leader cells, detailing emerging evidence on the hybrid epithelial-mesenchymal transition (EMT) state and the phenotypical plasticity exhibited by leader cells. Additionally, we explore the role of leader cells in chemotherapeutic resistance and immune evasion, highlighting their potential as effective and diverse targets for novel cancer therapies.
转移是癌症相关死亡的主要原因；然而，驱动转移级联的分子程序还不完全清楚。转移依赖于集体入侵——许多上皮癌利用这一发育过程来建立继发性肿瘤并促进广泛的疾病。集体入侵的关键驱动因素是“领导者细胞”，这是细胞的一个功能上不同的亚群，能够指导迁移、细胞收缩，并引导领先细胞、尾随细胞或跟随细胞。虽然大量研究集中在传统集体入侵背景下的领导者细胞生物学，但促进转移的领导者细胞的影响是一个新兴的研究领域。这篇综述深入探讨了领导者细胞的扩展作用，详细介绍了新兴的关于混合上皮-间充质转化（EMT）状态和领导者细胞表现出的表型可塑性的证据。此外，我们还探讨了领导者细胞在化疗耐药和免疫逃逸中的作用，强调了它们作为新型癌症治疗有效且多样化的靶标的潜力。
