Cited by 1,476MicroRNA in disease regulationExtracellular vesicles in diseaseBarrier Structure and Function Studies

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Cancer-Secreted miR-105 Destroys Vascular Endothelial Barriers to Promote Metastasis

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Zhou, Weiying, Fong, Miranda Y., Min, Yongfen, Somlo, George, Liu, Liang, Palomares, Melanie R., Yu, Yang, Chow, Amy, O’Connor, Sean Timothy Francis, Chin, Andrew R., Yen, Yun, Wang, Yafan, Marcusson, Eric G., Chu, Peiguo, Wu, Jun, Wu, Xiwei, Li, Arthur Xuejun, Li, Zhuo, Gao, Hanlin, Ren, Xiubao, Boldin, Mark P., Lin, Pengnian Charles, Wang, Shizhen Emily·2014·Cancer Cell

DOI 10.1016/j.ccr.2014.03.007PMC PMC4016197

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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.

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Authors: Zhou, W., Fong, M. Y., Min, Y., Somlo, G., Liu, L., Palomares, M. R., Yu, Y., Chow, A., O’Connor, S. T. F., Chin, A. R., Yen, Y., Wang, Y., Marcusson, E. G., Chu, P., Wu, J., Wu, X., Li, A. X., Li, Z., Gao, H., Ren, X., Boldin, M. P., Lin, P. C., & Wang, S. E.
Affiliations: City Of Hope National Medical Center (US)
National Cancer Institute (US)
Regulus Therapeutics (United States) (US)
Tianjin Medical University Cancer Institute and Hospital (CN)
Corresponding author: Wang, Shizhen Emily
ORCID: Zhou, Weiying
Liu, Liang
Palomares, Melanie R.
Yu, Yang
Chow, Amy
Yen, Yun
Wang, Yafan
Marcusson, Eric G.
Wu, Jun
Wu, Xiwei
Li, Zhuo
Gao, Hanlin
Ren, Xiubao
Boldin, Mark P.
Wang, Shizhen Emily
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2014-04
Volume: 25
Issue: 4
Pages: 501-515
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2014.03.007
PMC: PMC4016197
OpenAlex: W2143839116
Cited by: 1,476
References: 62
Citations by year: 2026: 61 · 2025: 91 · 2024: 113 · 2023: 145 · 2022: 164 · 2021: 175 · 2020: 148 · 2019: 152 · 2018: 118 · 2017: 111 · 2016: 97 · 2015: 72 · 2014: 28
FWCI: 32.89
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 378 d)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: American Association for Cancer Research
Breast Cancer Research Foundation (12-60-26-WANG)
Celgene
National Institutes of Health
National Key Research and Development Program of China (2012CB9333004)
National Cancer Institute (P30CA-33572, R01CA166020, R01CA163586, P30CA033572)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: miR-105, metastasis, breast cancer, ZO-1, tight junctions, endothelial barrier integrity, exosomes, vascular permeability, metastatic progression
MeSH terms: Breast Neoplasms, Cell Movement, Endothelium, Vascular, Female, Humans, Neoplasm Metastasis, Biomarkers, Tumor, MicroRNAs, Cell Line, Tumor, Cell Growth Processes

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Cancer-Secreted miR-105 Destroys Vascular Endothelial Barriers to Promote Metastasis

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