Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells.

Published

Journal Article

Cancer and other cells residing in the same niche engage various modes of interactions to synchronize and buffer the negative effects of environmental changes. Extracellular microRNAs (miRNAs) have recently been implicated in the intercellular crosstalk. Here we show a mechanistic model involving breast-cancer-secreted, extracellular-vesicle-encapsulated miR-105, which is induced by the oncoprotein MYC in cancer cells and, in turn, activates MYC signalling in cancer-associated fibroblasts (CAFs) to induce a metabolic program. This results in the capacity of CAFs to display different metabolic features in response to changes in the metabolic environment. When nutrients are sufficient, miR-105-reprogrammed CAFs enhance glucose and glutamine metabolism to fuel adjacent cancer cells. When nutrient levels are low and metabolic by-products accumulate, these CAFs detoxify metabolic wastes, including lactic acid and ammonium, by converting them into energy-rich metabolites. Thus, the miR-105-mediated metabolic reprogramming of stromal cells contributes to sustained tumour growth by conditioning the shared metabolic environment.

Full Text

Duke Authors

Cited Authors

  • Yan, W; Wu, X; Zhou, W; Fong, MY; Cao, M; Liu, J; Liu, X; Chen, C-H; Fadare, O; Pizzo, DP; Wu, J; Liu, L; Liu, X; Chin, AR; Ren, X; Chen, Y; Locasale, JW; Wang, SE

Published Date

  • May 2018

Published In

Volume / Issue

  • 20 / 5

Start / End Page

  • 597 - 609

PubMed ID

  • 29662176

Pubmed Central ID

  • 29662176

Electronic International Standard Serial Number (EISSN)

  • 1476-4679

Digital Object Identifier (DOI)

  • 10.1038/s41556-018-0083-6

Language

  • eng

Conference Location

  • England