期刊
NATURE
卷 534, 期 7607, 页码 335-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature18282
关键词
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资金
- Cancer Research UK
- Worldwide Cancer Research
- Medical Research Council (MRC)
- European Research Council
- EMBO
- Wellcome Trust
- MRC
- British Skin Foundation [5010] Funding Source: researchfish
- Cancer Research UK [15181] Funding Source: researchfish
- Medical Research Council [G0801904, MR/M01939X/1, MC_PC_12009] Funding Source: researchfish
- MRC [G0801904, MR/M01939X/1] Funding Source: UKRI
Whether protein synthesis and cellular stress response pathways interact to control stem cell function is currently unknown. Here we show that mouse skin stem cells synthesize less protein than their immediate progenitors in vivo, even when forced to proliferate. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translational programmes that together promote stem cell functions and tumorigenesis. Mechanistically, we show that inhibition of post-transcriptional cytosine-5 methylation locks tumour-initiating cells in this distinct translational inhibition programme. Paradoxically, this inhibition renders stem cells hypersensitive to cytotoxic stress, as tumour regeneration after treatment with 5-fluorouracil is blocked. Thus, stem cells must revoke translation inhibition pathways to regenerate a tissue or tumour.
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