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Cited by 200MicroRNA in disease regulationCancer Cells and MetastasisTGF-β signaling in diseases

Stromal miR-200s contribute to breast cancer cell invasion through CAF activation and ECM remodeling

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Tang, X, Hou, Y, Yang, G, Wang, X, Tang, S, Du, Y-E, Yang, L, Yu, T +5 more·2016·Cell Death & Differentiation
DOI 10.1038/cdd.2015.78PMC PMC4815985
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Abstract

The activation of cancer-associated fibroblasts (CAFs) is a key event in tumor progression, and alternative extracellular matrix (ECM) proteins derived from CAFs induce ECM remodeling and cancer cell invasion. Here we found that miR-200 s, which are generally downregulated in activated CAFs in breast cancer tissues and in normal fibroblasts (NFs) activated by breast cancer cells, are direct mediators of NF reprogramming into CAFs and of ECM remodeling. NFs with downregulated miR-200 s displayed the traits of activated CAFs, including accelerated migration and invasion. Ectopic expression of miR-200 s in CAFs at least partially restored the phenotypes of NFs. CAF activation may be governed by the targets of miR-200 s, Fli-1 and TCF12, which are responsible for cell development and differentiation; Fli-1 and TCF12 were obviously elevated in CAFs. Furthermore, miR-200 s and their targets influenced collagen contraction by CAFs. The upregulation of fibronectin and lysyl oxidase directly by miR-200 or indirectly through Fli-1 or TCF12 contributed to ECM remodeling, triggering the invasion and metastasis of breast cancer cells both in vitro and vivo. Thus, these data provide important and novel insights into breast CAF activation and ECM remodeling, which trigger tumor cell invasion.

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  • CAFs produce matrix-crosslinking enzymes and, together with force-mediated ECM remodelling, these contribute to increased stiffness of tumour tissue.

    “CAFs also produce matrix-crosslinking enzymes and, together with force-mediated ECM remodelling (reviewed in detail85,86), these contribute to the increased stiffness of tumour tissue87–89.”

    From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [88]

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Cited by

Sorted by citations

Authors
Tang, X., Hou, Y., Yang, G., Wang, X., Tang, S., Du, Y.-E., Yang, L., Yu, T., Zhang, H., Zhou, M., Wen, S., Xu, L., & Liu, M.
Affiliations
  • Chongqing Medical University (CN)
  • The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
  • Second Affiliated Hospital of Chongqing Medical University (CN)
Corresponding author
Liu, M
ORCID
Venue
Cell Death & Differentiation
Publisher
Springer Science and Business Media LLC
Published
2015-06-12
Volume
23
Issue
1
Pages
132-145
ISSN
  • 1350-9047 (ISSN-L)
  • 1476-5403
DOI
10.1038/cdd.2015.78
PMC
PMC4815985
OpenAlex
W1598296711
Cited by
200
References
4
Citations by year
2026: 10 · 2025: 9 · 2024: 41 · 2023: 21 · 2022: 16 · 2021: 23 · 2020: 18 · 2019: 16 · 2018: 13 · 2017: 13 · 2016: 19 · 2015: 1
FWCI
5.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Differentiation (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81472476, NSFC81472476, NSFC 81072147, NSFC 81402180)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
miR-200 family, breast cancer, cancer-associated fibroblasts, tumor invasion, extracellular matrix remodeling, FLI1, TCF12, fibronectin, lysyl oxidase, collagen contraction, metastasis, tumor microenvironment
MeSH terms
Breast Neoplasms, Cell Movement, Extracellular Matrix, Female, Fibroblasts, Fibronectins, Humans, Lung Neoplasms, Protein-Lysine 6-Oxidase, Microfilament Proteins, Neoplasm Invasiveness, Trans-Activators, Gene Expression Regulation, Neoplastic, Receptors, Cytoplasmic and Nuclear, MicroRNAs, Cell Proliferation, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors, Tumor Microenvironment, Heterografts

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