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Cancer stem cells: The challenges ahead

Cancer stem cells (CSCs) have been proposed as the driving force of tumorigenesis and the seeds of metastases. However, their existence and role remain a topic of intense debate. Recently, the identification of CSCs in endogenously developing mouse tumours has provided further support for this concept. Here I discuss the challenges in identifying CSCs, their dependency on a supportive niche and their role in metastasis, and propose that stemness is a flexible — rather than fixed — quality of tumour cells that can be lost and gained.

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Figure 1: CSC hierarchy in a tumour depends on niche factors and mutations.
Figure 2: De-differentiation and EMT confer cancer stemness and enhance the propensity for metastasis.

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Acknowledgements

Thanks to Felipe de Sousa e Melo for carefully reading the manuscript and suggesting changes. Apologies to all authors whose invaluable work is not mentioned or cited. This does not reflect a judgment on the work's quality, but is a result of space limitation. J.P.M. is supported by grants from the Dutch Cancer Society (UvA2009-4416, 2012-5612) and the Dutch Science Organization (VICI program).

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Correspondence to Jan Paul Medema.

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Medema, J. Cancer stem cells: The challenges ahead. Nat Cell Biol 15, 338–344 (2013). https://doi.org/10.1038/ncb2717

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