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Cited by 995Extracellular vesicles in diseaseMicroRNA in disease regulationCancer Cells and Metastasis

Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer

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Fang, Tian, Lv, Hongwei, Lv, Guishuai, Li, Ting, Wang, Changzheng, Han, Qin, Yu, Lexing, Su, Bo +8 more·2018·Nature Communications
DOI 10.1038/s41467-017-02583-0PMC PMC5768693
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Abstract

The communication between tumor-derived elements and stroma in the metastatic niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms tumor cells use to control metastatic niche formation are not fully understood. Here we report that in the lung metastatic niche, high-metastatic hepatocellular carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high-metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of β1-integrin-NF-κB signaling in fibroblasts. Activated CAFs further promote cancer progression by secreting pro-inflammatory cytokines, including IL-6 and IL-8. Clinical data show high serum exosomal miR-1247-3p levels correlate with lung metastasis in HCC patients. These results demonstrate intercellular crosstalk between tumor cells and fibroblasts is mediated by tumor-derived exosomes that control lung metastasis of HCC, providing potential targets for prevention and treatment of cancer metastasis.

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  • Exosomal miR-1247-3p secreted by hepatocellular carcinoma activates beta1-integrin-NF-κB signaling in fibroblasts, resulting in the production of pro-inflammatory cytokines, including IL-6 and IL-8.

    “Exosomal miR-1247-3p secreted by hepatocellular carcinoma activates beta1-integrin–NF-κB signaling in fibroblasts, resulting in the production of pro-inflammatory cytokines, including IL-6 and IL-8 (323).”

    From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [323]

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Cited by

Sorted by citations

Authors
Fang, T., Lv, H., Lv, G., Li, T., Wang, C., Han, Q., Yu, L., Su, B., Guo, L., Huang, S., Cao, D., Tang, L., Tang, S., Wu, M., Yang, W., & Wang, H.
Affiliations
  • Second Military Medical University (CN)
  • Tongji University (CN)
Corresponding author
  • Yang, Wen
  • Wang, Hongyang
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-01-15
Volume
9
Issue
1
Pages
191-191
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-017-02583-0
PMC
PMC5768693
OpenAlex
W2783562764
Cited by
995
References
5
Citations by year
2026: 41 · 2025: 90 · 2024: 125 · 2023: 168 · 2022: 160 · 2021: 155 · 2020: 142 · 2019: 73 · 2018: 40 · 2017: 1
FWCI
36.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81221061, 81622039, 81522035, 81372356, 81572895)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
exosomes, cancer-associated fibroblasts, hepatocellular carcinoma, lung metastasis, beta1 integrin, NF-κB signaling, metastatic niche, interleukin-6, interleukin-8, serum microRNA biomarker
MeSH terms
Cancer-Associated Fibroblasts, Animals, Cell Communication, Cell Transformation, Neoplastic, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Lung Neoplasms, Male, Mice, Nude, N-Acetyllactosamine Synthase, Neoplastic Cells, Circulating, Neoplasm Invasiveness, Neoplasm Transplantation, Signal Transduction, Interleukin-6, Gene Expression Regulation, Neoplastic, Interleukin-8, Integrin beta1, MicroRNAs, Cell Line, Tumor, Mice, Exosomes

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