Journal
NATURE CELL BIOLOGY
Volume 21, Issue 4, Pages 498-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41556-019-0299-0
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Funding
- Natural Science Foundation of China [81490750, 81720108029, 81621004, 81622036 81472468, 81672614, 81802645]
- National Key Research and Development Program of China [2016YFC1302300, 2017YFA0106300]
- Guangdong Science and Technology Department [2016B030229004, 2017B030314026]
- Science Foundation of Guangdong Province [2016A030306023, 2017A030313878, 201710010083]
- Guangzhou Science Technology and Innovation Commission [201803040015, 201508020008, 201508020249]
- Tip-top Scientific and Technical Innovative Youth Talents of Guangdong Special Support Program [2016TQ03R553]
- Fountain-Valley Life Sciences Fund of the University of Chinese Academy of Sciences Education Foundation
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Metabolic reprogramming is a hallmark of cancer. Here, we demonstrate that tumour-associated macrophages (TAMs) enhance the aerobic glycolysis and apoptotic resistance of breast cancer cells via the extracellular vesicle (EV) transmission of a myeloid-specific IncRNA, HIF-1 alpha-stabilizing long noncoding RNA (HISLA). Mechanistically, HISLA blocks the interaction of PHD2 and HIF-1 alpha to inhibit the hydroxylation and degradation of HIF-1 alpha. Reciprocally, lactate released from glycolytic tumour cells upregulates HISLA in macrophages, constituting a feed-forward loop between TAMs and tumour cells. Blocking EV-transmitted HISLA inhibits the glycolysis and chemoresistance of breast cancer in vivo. Clinically, HISLA expression in TAMs is associated with glycolysis, poor chemotherapeutic response and shorter survival of patients with breast cancer. Our study highlights the potential of IncRNAs as signal transducers that are transmitted between immune and tumour cells via EVs to promote cancer aerobic glycolysis.
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