期刊
NATURE CELL BIOLOGY
卷 17, 期 2, 页码 183-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3094
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资金
- United States Army Research and Material Command [W81-14-1-0029]
- National Institutes of Health (NIH)/National Cancer Institute (NCI) [R01CA166020, R01CA163586]
- California Breast Cancer Research Program [20IB-0118]
- Breast Cancer Research Foundation-AACR [12-60-26-WANG]
- City of Hope Women's Cancer Program
- NIH/NCI [P30CA33572]
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.
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