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Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells

Open access
Yan, Wei, Wu, Xiwei, Zhou, Weiying, Fong, Miranda Y., Cao, Minghui, Liu, Juan, Liu, Xiaojing, Chen, Chih-Hong, Fadare, Oluwole, Pizzo, Donald P., Wu, Jiawen, Liu, Liang, Liu, Xuxiang, Chin, Andrew R., Ren, Xiubao, Chen, Yuan, Locasale, Jason W., Wang, Shizhen Emily·2018·Nature Cell Biology

Abstract

Cancer and other cells residing in the same niche engage various modes of interactions to synchronize and buffer the negative effects of environmental changes. Extracellular microRNAs (miRNAs) have recently been implicated in the intercellular crosstalk. Here we show a mechanistic model involving breast-cancer-secreted, extracellular-vesicle-encapsulated miR-105, which is induced by the oncoprotein MYC in cancer cells and, in turn, activates MYC signalling in cancer-associated fibroblasts (CAFs) to induce a metabolic program. This results in the capacity of CAFs to display different metabolic features in response to changes in the metabolic environment. When nutrients are sufficient, miR-105-reprogrammed CAFs enhance glucose and glutamine metabolism to fuel adjacent cancer cells. When nutrient levels are low and metabolic by-products accumulate, these CAFs detoxify metabolic wastes, including lactic acid and ammonium, by converting them into energy-rich metabolites. Thus, the miR-105-mediated metabolic reprogramming of stromal cells contributes to sustained tumour growth by conditioning the shared metabolic environment. Consistent crosstalk between cancer cells and stromal cells exists in the tumour microenvironment. Yan et al. show that exosomal miR-105 derived from cancer cells confers metabolic plasticity in recipient cancer-associated fibroblasts to adapt to nutrient-replete and -deplete conditions, thereby sustaining tumour growth.

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Metadata

Authors
Yan, W., Wu, X., Zhou, W., Fong, M. Y., Cao, M., Liu, J., Liu, X., Chen, C.-H., Fadare, O., Pizzo, D. P., Wu, J., Liu, L., Liu, X., Chin, A. R., Ren, X., Chen, Y., Locasale, J. W., & Wang, S. E.
Venue
Nature Cell Biology
Published
2018-04-16
Volume
20
Issue
5
Pages
597-609
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
OpenAlex
W2797145001
Cited by
469
References
64
FWCI
16.24
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells. https://app.cochat.ai/papers/10.1038/s41556-018-0083-6
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Yan, W., Wu, X., Zhou, W., Fong, M. Y., Cao, M., Liu, J., Liu, X., Chen, C.-H., Fadare, O., Pizzo, D. P., Wu, J., Liu, L., Liu, X., Chin, A. R., Ren, X., Chen, Y., Locasale, J. W., & Wang, S. E. (2018). Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells. Nature Cell Biology. https://doi.org/10.1038/s41556-018-0083-6

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