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Metastatic niche functions and therapeutic opportunities

Abstract

Metastasis is an inefficient process, especially during colonization at a distant organ. This bottleneck underlies the importance of the metastatic niche for seeding and outgrowth of metastases. Here, we classify the common functions of different metastatic niches: anchorage, survival support, protection from external insults, licensing proliferation and outgrowth. We highlight the emerging role of the metastatic niche in maintaining cancer stemness and promoting immune evasion, and discuss therapeutic opportunities against the metastatic niche.

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Fig. 1: The four pillars of metastatic niche functions.
Fig. 2: Niche regulation of stemness, EMT/MET and cell plasticity in distant sites.
Fig. 3: Therapeutic targeting of the metastatic niche functions.

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Acknowledgements

We thank members of our laboratories for helpful discussions, and in particular, D. Liu for critical reading of the manuscript. We also apologize to the many investigators whose important studies could not be cited directly here owing to space limitations. The work was supported by a Susan G. Komen Fellowship (PDF15332075) and from Instituto de Salud Carlos III-FSE (MS17/00037) to T. C-T, and grants from the Brewster Foundation, the Breast Cancer Research Foundation, Department of Defense (BC123187), and the National Institutes of Health (R01CA141062) to Y.K.

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Celià-Terrassa, T., Kang, Y. Metastatic niche functions and therapeutic opportunities. Nat Cell Biol 20, 868–877 (2018). https://doi.org/10.1038/s41556-018-0145-9

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