title: Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis.
abstract: Reprogrammed glucose metabolism as a result of increased glycolysis and glucose uptake is a hallmark of cancer. Here we show that cancer cells can suppress glucose uptake by non-tumour cells in the premetastatic niche, by secreting vesicles that carry high levels of the miR-122 microRNA. High miR-122 levels in the circulation have been associated with metastasis in breast cancer patients, and we show that cancer-cell-secreted miR-122 facilitates metastasis by increasing nutrient availability in the premetastatic niche. Mechanistically, cancer-cell-derived miR-122 suppresses glucose uptake by niche cells in vitro and in vivo by downregulating the glycolytic enzyme pyruvate kinase. In vivo inhibition of miR-122 restores glucose uptake in distant organs, including brain and lungs, and decreases the incidence of metastasis. These results demonstrate that, by modifying glucose utilization by recipient premetastatic niche cells, cancer-derived extracellular miR-122 is able to reprogram systemic energy metabolism to facilitate disease progression.
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Miranda Y
authors.initials: MY
authors.lastname: Fong
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Weiying
authors.initials: W
authors.lastname: Zhou
authors.affiliation: 1] Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA [2] Department of Biotherapy and Key Laboratory of Cancer Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Molecular Medicine, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Aileen Y
authors.initials: AY
authors.lastname: Alontaga
authors.affiliation: 1] Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA [2] City of Hope Irell &Manella Graduate School of Biological Sciences, Duarte, California 91010, USA.
authors.forename: Manasa
authors.initials: M
authors.lastname: Chandra
authors.affiliation: Department of Chemistry, University of California, Riverside, California 92521, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ashby
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Chow
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Sean Timothy Francis
authors.initials: ST
authors.lastname: O'Connor
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Shasha
authors.initials: S
authors.lastname: Li
authors.affiliation: 1] Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA [2] City of Hope Irell &Manella Graduate School of Biological Sciences, Duarte, California 91010, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Chin
authors.affiliation: Department of Medical Oncology, City of Hope Medical Center, Duarte, California 91010, USA.
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.affiliation: 1] Department of Medical Oncology, City of Hope Medical Center, Duarte, California 91010, USA [2] Department of Population Sciences, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Palomares
authors.affiliation: Core of Electron Microscopy, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: 1] Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA [2] City of Hope Irell &Manella Graduate School of Biological Sciences, Duarte, California 91010, USA.
authors.forename: Jacob R
authors.initials: JR
authors.lastname: Tremblay
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuyada
authors.affiliation: Department of Neurosciences, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Reid
authors.affiliation: Core of Integrative Genomics, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Core of Synthetic and Biopolymer Chemistry, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
authors.forename: Piotr
authors.initials: P
authors.lastname: Swiderski
authors.affiliation: Department of Biotherapy and Key Laboratory of Cancer Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Xiubao
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Neurosciences, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Kong
authors.affiliation: Department of Chemistry, University of California, Riverside, California 92521, USA.
authors.forename: Wenwan
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Molecular Medicine, City of Hope Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1] Department of Cancer Biology, City of Hope Beckman Research Institute, Duarte, California 91010, USA [2] Department of Biotherapy and Key Laboratory of Cancer Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Shizhen Emily
authors.initials: SE
authors.lastname: Wang
mesh_terms: D001253:Astrocytes / Q000378:metabolism; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D001973:Bromodeoxyuridine / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D055354:Exosomes / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D011770:Pyruvate Kinase / Q000378:metabolism
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D008156:Luciferases; D011770:Pyruvate Kinase; D001973:Bromodeoxyuridine; D005947:Glucose