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

Abstract

Cancer and other cells residing in the same niche engage various modes of interactions to synchronize and to buffer the negative effects of environmental changes. Extracellular miRNAs have been recently 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 signaling in cancer-associated fibroblasts (CAFs) to induce a metabolic program. This results in CAFs’ capacity 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 nutrients are deprived whereas metabolic byproducts are accumulated, 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.

Exosomes Derived from Human Primary and Metastatic Colorectal Cancer Cells Contribute to Functional Heterogeneity of Activated Fibroblasts by Reprogramming Their Proteome

“…This suggests that tumor‐derived Exos metabolically alter the activated fibroblasts and potentially contribute toward metabolite sharing between tumor and CAFs that is critical for tumor progression . The role of cancer Exos in metabolic reprogramming of stromal fibroblasts is only beginning to emerge . Breast cancer Exos have been shown to reprogram glucose metabolism in pre‐metastatic cells to promote metastasis .…”

Tumoral microvesicle–activated glycometabolic reprogramming in fibroblasts promotes the progression of oral squamous cell carcinoma

“…In ourprevious study, we performed a Kyoto Encyclopedia of Genes and Genomes pathway analysis of overlapping proteins in TMVs and found that proteins involved in metabolic pathways were the most abundant (11). Although the roles of cancer microenvironment–derived MVs in modulating cancer cell metabolism have been reported, the role of TMVs in stromal metabolic reprogramming was less studied (24–27). Thus, we examined the role of TMVs in modulating stromal metabolic alteration in the current study.…”

A positive feedback loop between ZNF205‐AS1 and EGR4 promotes non‐small cell lung cancer growth

“…We further verified that ZNF205‐AS1 increased EGR4 mRNA stability, and therefore up‐regulated EGR4 expression. microRNAs (miRNAs) are well‐known to bind the 3’UTR of target mRNAs and induce the degradation and/or translation inhibition of target mRNAs . The interaction between ZNF205‐AS1 transcript and EGR4 mRNA 3’UTR may protect EGR4 mRNA from miRNAs‐induced degradation, which need further investigation.…”