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Breast cancer-derived exosomes regulate cell invasion and metastasis in breast cancer via miR-146a to activate cancer associated fibroblasts in tumor microenvironment

Yang, Shan-Shan, Ma, Shuang, Dou, He, Liu, Feng, Zhang, Shi-Yuan, Jiang, Cong, Xiao, Min, Huang, Yuan-Xi·2020·Experimental Cell Research

Abstract

OBJECTIVE To explore the effects of breast cancer (BC)-derived exosomes on invasion and migration of BC cells. METHODS Exosomes (Exo-MA, Exo-M7, Exo-M1) were extracted from normal breast epithelial cells (MCF-10A), BC cells (MCF-7/MDA-MB-231) and BC cells with miR-146a overexpression or knockdown using multi-step differential centrifugation. Morphologies and sizes of exosomes were observed by transmission electron microscope (TEM) and particle size analysis respectively. BC mouse models were injected with DIR labeled Exo-MA, Exo-M7 or Exo-M1. The epithelial-mesenchymal transition (EMT) in BC cells was determined by PCR and Western blot. PKH67 labeled Exo-MA, Exo-M7 and Exo-M1 were incubated with NFs or MCF-7 to measure the activation of CAFs. Cell invasion and migration abilities were determined by scratch test and Transwell assay. RESULTS Exo-MA, Exo-M7, Exo-M1 were successfully extracted with positive expressions of Alix, CD63 and TSG101. Contents of Ki67, N-cadherin, Vimentin and Snail-1 were increased but E-cadherin was decreased, compared to Exo-MA group. Exo-M7 or Exo-M1 could increase BC cell proliferation and enhance EMT in nude mouse. Exo-M7 and Exo-M1 could accelerate the transformation of NFs into CAFs and promote the recruitment of CAFs in MCF-7. Transfection of miR-146a could promote the transformation of NFs into CAFs and promote cell invasion and migration of MCF-7 cells. As a target gene of miR-146a, TXNIP could inhibit the activation of CAFs. miR-146a overexpression or TXNIP silence enhance the activation of Wnt signal pathway. CONCLUSION BC-derived exosomes promote the activation of CAFs through miR-146a/TXNIP axis to activate Wnt pathway, which in turn enhances invasion and metastasis of BC cells.

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Metadata

Authors
Yang, S.-S., Ma, S., Dou, H., Liu, F., Zhang, S.-Y., Jiang, C., Xiao, M., & Huang, Y.-X.
Venue
Experimental Cell Research
Publisher
Elsevier BV
Published
2020-06
Volume
391
Issue
2
Pages
111983
ISSN
0014-4827 (ISSN-L)
OpenAlex
W3014687098
Cited by
169
References
7
FWCI
7.33
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Breast cancer-derived exosomes regulate cell invasion and metastasis in breast cancer via miR-146a to activate cancer associated fibroblasts in tumor microenvironment. https://app.cochat.ai/papers/10.1016/j.yexcr.2020.111983
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Yang, S.-S., Ma, S., Dou, H., Liu, F., Zhang, S.-Y., Jiang, C., Xiao, M., & Huang, Y.-X. (2020). Breast cancer-derived exosomes regulate cell invasion and metastasis in breast cancer via miR-146a to activate cancer associated fibroblasts in tumor microenvironment. Experimental Cell Research. https://doi.org/10.1016/j.yexcr.2020.111983

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