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Cancer Cell. 2014 Apr 14;25(4):501-15. doi: 10.1016/j.ccr.2014.03.007.

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

Author information

1
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.
2
Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
3
Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
4
Department of Medical Oncology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
5
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.
6
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.
7
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.
8
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.
9
Core of Translational Research Laboratory, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
10
Oncology and Basic Mechanisms, Regulus Therapeutics, San Diego, CA 92121, USA.
11
Department of Pathology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
12
Department of Comparative Medicine, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
13
Core of Integrative Genomics, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
14
Department of Information Science, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
15
Core of Electron Microscopy, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
16
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.
17
Department of Biotherapy and Key Laboratory of Cancer Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
18
Department of Molecular and Cellular Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
19
Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA. Electronic address: ewang@coh.org.

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.

PMID:
24735924
PMCID:
PMC4016197
DOI:
10.1016/j.ccr.2014.03.007
[Indexed for MEDLINE]
Free PMC Article
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