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

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 metabolic plasticity toenhance glycolysis and glutaminolysis to fuel adjacent cancer cells when nutrients are sufficient (the symbiosis mode), and detoxify metabolic wastes (lactic acid and ammonium) by converting them into energy-rich metabolites, when nutrients are deprived whereas metabolic byproducts are accumulated. This commensalism of cancer stroma emphasizes the functional flexibility of non-cancer cell populations contributing to cancer fitness during sustained growth of tumour.