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Decoding leader cells in collective cancer invasion

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NATURE REVIEWS CANCER
卷 21, 期 9, 页码 592-604

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NATURE PORTFOLIO
DOI: 10.1038/s41568-021-00376-8

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  1. National Science Foundation Center for Theoretical Biological Physics [PHY-2019745, CHE-1614101, PHY-1605817, CBET-1802947]
  2. Simons Foundation [594598]
  3. Ramanujan Fellowship by SERB, DST, Government of India [SB/S2/RJN-049/2018]

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Collective cancer cell invasion with leader-follower organization is a key mechanism of metastasis, but a consensus definition of leader cell characteristics is lacking. This Perspective outlines a conceptual framework for understanding how leader cells coordinate the invasion process using a multitude of cellular and molecular programmes.
Collective cancer invasion with leader-follower organization is increasingly recognized as a predominant mechanism in the metastatic cascade. Leader cells support cancer invasion by creating invasion tracks, sensing environmental cues and coordinating with follower cells biochemically and biomechanically. With the latest developments in experimental and computational models and analysis techniques, the range of specific traits and features of leader cells reported in the literature is rapidly expanding. Yet, despite their importance, there is no consensus on how leader cells arise or their essential characteristics. In this Perspective, we propose a framework for defining the essential aspects of leader cells and provide a unifying perspective on the varying cellular and molecular programmes that are adopted by each leader cell subtype to accomplish their functions. This Perspective can lead to more effective strategies to interdict a major contributor to metastatic capability. Collective cancer cell invasion with leader-follower organization is a key mechanism of metastasis, but a consensus definition of leader cell characteristics is lacking. This Perspective outlines a conceptual framework for understanding how leader cells coordinate the invasion process using a multitude of cellular and molecular programmes.

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