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

被引：1060

作者：

Fong, Miranda Y. ^{[1
]}

Zhou, Weiying ^{[1
]}

Liu, Liang ^{[1
,2
,3
]}

Alontaga, Aileen Y. ^{[4
]}

Chandra, Manasa ^{[1
,5
]}

Ashby, Jonathan ^{[6
]}

Chow, Amy ^{[1
]}

O'Connor, Sean Timothy Francis ^{[1
]}

Li, Shasha ^{[1
]}

Chin, Andrew R. ^{[1
,5
]}

Somlo, George ^{[7
]}

Palomares, Melanie ^{[7
,8
]}

Li, Zhuo ^{[9
]}

Tremblay, Jacob R. ^{[1
,5
]}

Tsuyada, Akihiro ^{[1
]}

Sun, Guoqiang ^{[10
]}

Reid, Michael A. ^{[1
]}

Wu, Xiwei ^{[11
]}

Swiderski, Piotr ^{[12
]}

Ren, Xiubao ^{[2
,3
]}

Shi, Yanhong ^{[10
]}

Kong, Mei ^{[1
]}

Zhong, Wenwan ^{[6
]}

Chen, Yuan ^{[4
]}

Wang, Shizhen Emily ^{[1
,2
,3
]}

机构：

[1] City Hope Beckman Res Inst, Dept Canc Biol, Duarte, CA 91010 USA

[2] Tianjin Med Univ Canc Inst & Hosp, Dept Biotherapy, Tianjin 300060, Peoples R China

[3] Tianjin Med Univ Canc Inst & Hosp, Key Lab Canc Immunol, Tianjin 300060, Peoples R China

[4] City Hope Beckman Res Inst, Dept Mol Med, Duarte, CA 91010 USA

[5] City Hope Irell & Manella Grad Sch Biol Sci, Duarte, CA 91010 USA

[6] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA

[7] City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA

[8] City Hope Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA

[9] City Hope Comprehens Canc Ctr, Core Electron Microscopy, Duarte, CA 91010 USA

[10] City Hope Beckman Res Inst, Dept Neurosci, Duarte, CA 91010 USA

[11] City Hope Comprehens Canc Ctr, Core Integrat Genom, Duarte, CA 91010 USA

[12] City Hope Comprehens Canc Ctr, Core Synthet & Biopolymer Chem, Duarte, CA 91010 USA

来源：

NATURE CELL BIOLOGY | 2015年 / 17卷 / 02期

基金：

美国国家卫生研究院;

关键词：

PYRUVATE-KINASE M2; CIRCULATING MICRORNAS; MESSENGER-RNAS; GENE-TRANSCRIPTION; UP-REGULATION; IN-SITU; CELLS; FIBROBLASTS; TRANSPORT; EXOSOMES;

D O I：

10.1038/ncb3094

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：183 / +

页数：20

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