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Nat Cell Biol. 2015 Feb;17(2):183-94. doi: 10.1038/ncb3094. Epub 2015 Jan 26.

Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis.

Author information

1
Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
2
1] Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA [2] Department of Biotherapy and Key Laboratory of Cancer Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
3
Department of Molecular Medicine, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
4
1] Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA [2] City of Hope Irell &Manella Graduate School of Biological Sciences, Duarte, California 91010, USA.
5
Department of Chemistry, University of California, Riverside, California 92521, USA.
6
Department of Medical Oncology, City of Hope Medical Center, Duarte, California 91010, USA.
7
1] Department of Medical Oncology, City of Hope Medical Center, Duarte, California 91010, USA [2] Department of Population Sciences, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
8
Core of Electron Microscopy, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
9
Department of Neurosciences, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
10
Core of Integrative Genomics, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
11
Core of Synthetic and Biopolymer Chemistry, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
12
Department of Biotherapy and Key Laboratory of Cancer Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

Abstract

Reprogrammed glucose metabolism as a result of increased glycolysis and glucose uptake is a hallmark of cancer. Here we show that cancer cells can suppress glucose uptake by non-tumour cells in the premetastatic niche, by secreting vesicles that carry high levels of the miR-122 microRNA. High miR-122 levels in the circulation have been associated with metastasis in breast cancer patients, and we show that cancer-cell-secreted miR-122 facilitates metastasis by increasing nutrient availability in the premetastatic niche. Mechanistically, cancer-cell-derived miR-122 suppresses glucose uptake by niche cells in vitro and in vivo by downregulating the glycolytic enzyme pyruvate kinase. In vivo inhibition of miR-122 restores glucose uptake in distant organs, including brain and lungs, and decreases the incidence of metastasis. These results demonstrate that, by modifying glucose utilization by recipient premetastatic niche cells, cancer-derived extracellular miR-122 is able to reprogram systemic energy metabolism to facilitate disease progression.

PMID:
25621950
PMCID:
PMC4380143
DOI:
10.1038/ncb3094
[Indexed for MEDLINE]
Free PMC Article
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