The study investigates the role of miR-122 in breast cancer metastasis. It finds that cancer cells secrete high levels of miR-122, which suppresses glucose uptake by niche cells in the premetastatic niche, thereby increasing nutrient availability for cancer cells. Mechanistically, miR-122 downregulates the glycolytic enzyme pyruvate kinase (PKM) in both in vitro and in vivo models. Inhibition of miR-122 restores glucose uptake in distant organs and reduces metastasis. The findings suggest that cancer-derived extracellular miR-122 reprograms glucose metabolism to facilitate disease progression.The study investigates the role of miR-122 in breast cancer metastasis. It finds that cancer cells secrete high levels of miR-122, which suppresses glucose uptake by niche cells in the premetastatic niche, thereby increasing nutrient availability for cancer cells. Mechanistically, miR-122 downregulates the glycolytic enzyme pyruvate kinase (PKM) in both in vitro and in vivo models. Inhibition of miR-122 restores glucose uptake in distant organs and reduces metastasis. The findings suggest that cancer-derived extracellular miR-122 reprograms glucose metabolism to facilitate disease progression.