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Decoding leader cells in collective cancer invasion

Subjects

Abstract

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.

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Fig. 1: Leader cell categories and key functions.
Fig. 2: Path generation.
Fig. 3: Cell–cell coordination and guidance.
Fig. 4: Survival and metastasis.

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Acknowledgements

This work was supported by National Science Foundation Center for Theoretical Biological Physics PHY-2019745 (J.N.O., H.L.), CHE-1614101 (J.N.O.), PHY-1605817 (H.L.) and CBET-1802947 (P.K.W.). F.B. is also supported by a grant from the Simons Foundation (594598, QN). J.N.O. is a CPRIT Scholar in Cancer Research. M.K.J. is supported by a Ramanujan Fellowship (SB/S2/RJN-049/2018) awarded by SERB, DST, Government of India.

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P.K.W., S.A.V.M. and M.K.J. researched data for the article; all authors contributed to discussion of content, writing, reviewing and editing the manuscript.

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Vilchez Mercedes, S.A., Bocci, F., Levine, H. et al. Decoding leader cells in collective cancer invasion. Nat Rev Cancer 21, 592–604 (2021). https://doi.org/10.1038/s41568-021-00376-8

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