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Cancer-Secreted miR-105 Destroys Vascular Endothelial Barriers to Promote Metastasis
Open accessAbstract
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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“Many studies have also demonstrated that extracellular miRNAs can exert biological functions in recipient cells to regulate their activity, thereby acting as intercellular signaling molecules.”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [134]
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Guan, Y., Chen, L., Bao, Y., Li, Z., Cui, R., Li, G., & Wang, Y. (2015) · PubMed Central · Cited by 18
Hao, D., Li, Y., Zhao, G.-F., & Zhang, M. (2019) · Thoracic Cancer · doi:10.1111/1759-7714.13175 · Cited by 18
Exosomes in head and neck cancer. Updating and revisiting
Zorrilla, S. R., Garcı́a, A. G., Carrión, A. B., Vila, P. G., Martín, J. M. S., Gallas, M., & Pérez‐Sayáns, M. (2019) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2019.1662000 · Cited by 18
miR-452 promotes the development of gastric cancer via targeting EPB41L3
He, X., & Shu, Y. (2019) · Pathology - Research and Practice · doi:10.1016/j.prp.2019.152725 · Cited by 18
Purification Methods and the Presence of RNA in Virus Particles and Extracellular Vesicles
Zhou, Y., McNamara, R. P., & Dittmer, D. P. (2020) · Viruses · doi:10.3390/v12090917 · Cited by 18
MicroRNAs as paracrine signaling mediators in cancers and metabolic diseases
Matsuda, A., Yan, I. K., Foye, C., Parasramka, M. A., & Patel, T. C. (2016) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2016.07.005 · Cited by 20
Prostate cancer exosomes as modulators of the tumor microenvironment
Shephard, A. P., Yeung, V., Clayton, A., & Webber, J. P. (2017) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2017.32 · Cited by 19
“Metastatic breast cancer cells, for example, were shown to enhance vascular permeability, and promote tumor metastasis, via the suppression of the tight junction protein ZO-1 by exosome delivered miR105[70].”
BackgroundmicroRNAs and Personalized Medicine: Evaluating Their Potential as Cancer Biomarkers
Saumet, A., & Lecellier, C. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-22671-2_2 · Cited by 17
Exosomes: A rising star in breast cancer (Review)
Wang, L., Wang, B., Wen, H., Mao, J., Ren, Y., & Yang, H. (2020) · Oncology Reports · doi:10.3892/or.2020.7638 · Cited by 16
Organ-Specific Uptake of Extracellular Vesicles Secreted by Urological Cancer Cells
Linxweiler, J., Kolbinger, A., Himbert, D., Zeuschner, P., Saar, M., Stöckle, M., & Junker, K. (2021) · Cancers · doi:10.3390/cancers13194937 · Cited by 17
Extracellular vesicles: from bench to bedside
Chen, Y., & Yu, L. (2022) · Current Medicine · doi:10.1007/s44194-022-00001-2 · Cited by 16
Liu, Z., Zhang, N., Xin, B., Shi, Y., Liang, Z., Wan, Y., & Hu, X. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.123792 · Cited by 17
Exosomal miRNAs as novel avenues for breast cancer treatment
Singh, T., Kaushik, M. C., Mishra, L. C., Behl, C., Singh, V. P., & Tuli, H. S. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1134779 · Cited by 17
Cruz-Burgos, M., Cortés-Ramírez, S. A., Losada-García, A., Morales-Pacheco, M., Martínez‐Martínez, E., Morales-Montor, J. G., Haddad-Servín, A., Izquierdo-Luna, J. S., Martinez, G. R., Ramos‐Godínez, M. D. P., et al. (2023) · Cancers · doi:10.3390/cancers15164148 · Cited by 17
Potential roles of the exosome/microRNA axis in breast cancer
Mamalo, A. S., Alivirdiloo, V., Sadeghnejad, A., Hajiabbasi, M., Gargari, M. K., & Valilo, M. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.154845 · Cited by 17
Wang, J., Jiang, W., Liu, S., Shi, K., Zhang, Y., Chen, Y., Shan, J., Wang, Y., Xu, X., Li, C. X., et al. (2023) · Liver International · doi:10.1111/liv.15773 · Cited by 17
“15,16 22 Nevertheless, there is a lack of relevant studies to confirm that exosomes derived from CCA can affect the progression of tumour.”
BackgroundCirculating Tumour Cells in the Prediction of Bone Metastasis
Choi, S. W., Sun, A. K., Cheung, J. P. Y., & Ho, J. C. Y. (2024) · Cancers · doi:10.3390/cancers16020252 · Cited by 17
“Circulating tumour cells (from breast tumours), on their part have been shown to secrete angiogenic factors and microRNA-105, both of which can decrease the expression of tight junction proteins of the vascular endothelial layer [27].”
BackgroundThe role of microRNAs in brain metastasis
Hudson, K., Mondia, M. W. L., Zhang, Y., Saha, S., Gibert, M. K., Dube, C., Sun, Y., Marcinkiewicz, P., Fadul, C. E., & Abounader, R. (2024) · Journal of Neuro-Oncology · doi:10.1007/s11060-023-04541-x · Cited by 16
“Lastly, miR-105 was shown to directly target ZO-1, an important tight junction protein, in breast cancer BM [50].”
Background
Metadata
- 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
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 25
- Issue
- 4
- Pages
- 501-515
- ISSN
- 1535-6108 (ISSN-L)
- 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
- 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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