title: Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis.
abstract: Cancer-secreted microRNAs (miRNAs) are emerging mediators of cancer-host crosstalk. Here we show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in nonmetastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas inhibition of miR-105 in highly metastatic tumors alleviates these effects. miR-105 can be detected in the circulation at the premetastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer.
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing, 400038, China.
authors.forename: Weiying
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Miranda Y
authors.initials: MY
authors.lastname: Fong
authors.affiliation: Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Yongfen
authors.initials: Y
authors.lastname: Min
authors.affiliation: Department of Medical Oncology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; 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 Medical Oncology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; Department of Population Sciences, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Palomares
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; Department of Biotherapy and Key Laboratory of Cancer Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Chow
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 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 and Medical Center, Duarte, CA 91010, USA; City of Hope Irell & Manella Graduate School of Biological Sciences, Duarte, CA 91010, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Chin
authors.affiliation: Department of Molecular Pharmacology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; Core of Translational Research Laboratory, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.affiliation: Core of Translational Research Laboratory, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Yafan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Oncology and Basic Mechanisms, Regulus Therapeutics, San Diego, CA 92121, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Marcusson
authors.affiliation: Department of Pathology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Peiguo
authors.initials: P
authors.lastname: Chu
authors.affiliation: Department of Comparative Medicine, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Core of Integrative Genomics, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Information Science, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Arthur Xuejun
authors.initials: AX
authors.lastname: Li
authors.affiliation: Core of Electron Microscopy, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; Core of Integrative Genomics, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Hanlin
authors.initials: H
authors.lastname: Gao
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 Molecular and Cellular Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Boldin
authors.affiliation: Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Pengnian Charles
authors.initials: PC
authors.lastname: Lin
authors.affiliation: Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA. Electronic address: ewang@coh.org.
authors.forename: Shizhen Emily
authors.initials: SE
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis
chemical_list: D014408:Biomarkers, Tumor; C588223:MIRN105 microRNA, human; D035683:MicroRNAs
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