Role of Extracellular miR-122 in Breast Cancer Metastasis
Technical Report,15 Jan 2015,14 Jan 2016
Beckman Research Institute of the City of Hope Duarte United States
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Reprogrammed glucose metabolism due to increased glycolysis and glucose uptake is a hallmark of cancer. The purpose of this study is to study the role of cancer-secreted miR-122 in adapting the pre-metastatic niche through the down-regulation of the glycolytic enzyme pyruvate kinase M2 PKM2. We show that cancer cells can suppress glucose metabolism in lung fibroblasts and brain astrocyte niche cells through secreting extracellular miR-122, a miRNA whose level in the circulation predicts metastasis of breast cancer. Our results demonstrate that cancer cells are capable of reprogramming how niche cells metabolize glucose through exosome secretion of miR-122 and the consequent down-regulation of glucose metabolic enzymes in niche cells leading to reduced glucose utilization. In vivo treatment with anti-miR-122 oligos restores glucose uptake in distant organs, including brain and lungs, while decreasing the incidence of metastasis. Our results thereby demonstrate an important function of cancer-derived extracellular miR-122 in adapting glucose utilization of recipient niche cells, and thus reprograms systemic energy metabolism to facilitate disease progression.