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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Fong MY,Zhou W,Liu L,Alontaga AY,Chandra M,Ashby J,Chow A,O'Connor ST,Li S,Chin AR,Somlo G,Palomares M,Li Z,Tremblay JR,Tsuyada A,Sun G,Reid MA,Wu X,Swiderski P,Ren X,Shi Y,Kong M,Zhong W,Chen Y,Wang SEdoi
10.1038/ncb3094subject
Has Abstractpub_date
2015-02-01 00:00:00pages
183-94issue
2eissn
1465-7392issn
1476-4679pii
ncb3094journal_volume
17pub_type
杂志文章abstract::The spindle checkpoint ensures accurate chromosome segregation by delaying cell-cycle progression until all sister kinetochores capture microtubules from opposite poles and come under tension (for reviews, see refs 1, 2). Although the checkpoint is activated by either the lack of kinetochore-microtubule attachments or...
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