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Cell-intrinsic and microenvironmental determinants of metastatic colonization

A Publisher Correction to this article was published on 26 June 2024

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Abstract

Cancer metastasis is a biologically complex process that remains a major challenge in the oncology clinic, accounting for nearly all of the mortality associated with malignant neoplasms. To establish metastatic growths, carcinoma cells must disseminate from the primary tumour, survive in unfamiliar tissue microenvironments, re-activate programs of proliferation, and escape innate and adaptive immunosurveillance. The entire process is extremely inefficient and can occur over protracted timescales, yielding only a vanishingly small number of carcinoma cells that are able to complete all of the required steps. Here we review both the cancer-cell-intrinsic mechanisms and microenvironmental interactions that enable metastatic colonization. In particular, we highlight recent work on the behaviour of already-disseminated tumour cells, since meaningful progress in treating metastatic disease will clearly require a better understanding of the cells that spawn metastases, which generally have disseminated by the time of initial diagnosis.

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Fig. 1: The invasion–metastasis cascade.
Fig. 2: Survival and proliferation of DTCs.
Fig. 3: Immune escape.

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Acknowledgements

We would like to thank current and former members of the Weinberg laboratory for their scientific input. We also thank C. Rausch for illustration of the figures. Work in the Weinberg laboratory is supported by the Samuel Waxman Cancer Research Foundation, the Virginia and D. K. Ludwig Fund for Cancer Research, the Nile Albright Research Foundation, the National Institutes of Health (R35 CA220487), the Breast Cancer Research Foundation and the Koch Stem Cell Initiative. A.W.L. was supported by an American Cancer Society—New England Division—Ellison Foundation Postdoctoral Fellowship (PF-15-131-01-CSM) and a postdoctoral fellowship from the Ludwig Center at MIT. Y.Z. was supported by the CAMS Innovation Fund for Medical Sciences (2023-I2M-3-003 and 2022-I2M-1-008), the National Natural Science Foundation of China (82372750) and National Key R&D Program of China (2023YFC2507000).

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Lambert, A.W., Zhang, Y. & Weinberg, R.A. Cell-intrinsic and microenvironmental determinants of metastatic colonization. Nat Cell Biol 26, 687–697 (2024). https://doi.org/10.1038/s41556-024-01409-8

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