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PMID: 24735924 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis.

Cancer cell ·Vol. 25 ·No. 4 ·2014-04-14 ·Pages 501-15

Zhou W, Fong MY, Min Y, Somlo G, Liu L, Palomares MR, Yu Y, Chow A, O'Connor ST, Chin AR, Yen Y, Wang Y, Marcusson EG, Chu P, Wu J, Wu X, Li AX, Li Z, Gao H, Ren X, Boldin MP, Lin PC, Wang SE

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.

MeSH Terms
Biomarkers, Tumor/genetics,metabolism Breast Neoplasms/genetics,metabolism,pathology Cell Growth Processes/physiology Cell Line, Tumor Cell Movement Endothelium, Vascular/metabolism,pathology Female Humans MicroRNAs/genetics,metabolism Neoplasm Metastasis
Chemicals
Biomarkers, Tumor MIRN105 microRNA, human MicroRNAs
Authors & Affiliations
23 authors, click to expand affiliations / ORCID
Zhou Weiying
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.
Fong Miranda Y
Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
Min Yongfen
Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Somlo George
Department of Medical Oncology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
Liu Liang
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.
Palomares Melanie R
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.
Yu Yang
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.
Chow Amy
Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
O'Connor Sean Timothy Francis
Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
Chin Andrew R
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.
Yen Yun
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.
Wang Yafan
Core of Translational Research Laboratory, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
Marcusson Eric G
Oncology and Basic Mechanisms, Regulus Therapeutics, San Diego, CA 92121, USA.
Chu Peiguo
Department of Pathology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
Wu Jun
Department of Comparative Medicine, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
Wu Xiwei
Core of Integrative Genomics, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
Li Arthur Xuejun
Department of Information Science, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
Li Zhuo
Core of Electron Microscopy, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
Gao Hanlin
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.
Ren Xiubao
Department of Biotherapy and Key Laboratory of Cancer Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
Boldin Mark P
Department of Molecular and Cellular Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
Lin Pengnian Charles
Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Wang Shizhen Emily
Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA. Electronic address: ewang@coh.org.
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1878-3686
DOI
10.1016/j.ccr.2014.03.007
Email
ewang@coh.org
Published
2014-04-14
Pages
501-15
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC4016197
Subset
IM
Grants
NCI NIH HHS · R01CA163586 · United States
NCI NIH HHS · R01 CA166020 · United States
NCI NIH HHS · P30CA33572 · United States
NCI NIH HHS · R01 CA163586 · United States
NCI NIH HHS · R01CA166020 · United States
NCI NIH HHS · P30 CA033572 · United States
Databases
GEO
GSE50429
Corrections
CommentIn
PMID: 24776771
CommentIn
PMID: 24804958
CommentIn
PMID: 26181789
External Links
PubMed source DOI: 10.1016/j.ccr.2014.03.007 PMC Full Text View journal details
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