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

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 Biol

journal_title

Nature cell biology

authors

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 SE

doi

10.1038/ncb3094

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

183-94

issue

2

eissn

1465-7392

issn

1476-4679

pii

ncb3094

journal_volume

17

pub_type

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