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Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signalling
Abstract
We determined the molecular mechanism of inhibitory effect of human mesenchymal stem cells (hMSCs) on the growth of human MCF-7 breast cancer cells. Our finding showed that beta-catenin was down-regulated in MCF-7 cells by conditioned media from Z3 hMSCs, and the expression level of dickkopf-1 (Dkk-1) was higher in Z3 cells than that in MCF-7 cells. Neutralization of Dkk-1 and small interference RNA targeting Dkk-1 mRNA in Z3 cells attenuated the inhibitory effect of Z3 cells on MCF-7 cells. Overexpression of Dkk-1 in Z3 cells enhanced the inhibition. Therefore, Dkk-1 secreted by Z3 cells involves the inhibition via the Wnt pathway.
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“the disruption of the cancer-associated signaling pathways, such as PI3K/AKT [107], [113], via upregulation of PTEN, and of WNT/β-catenin signaling pathway by MSCs-secreted antagonist of the Wnt signaling DKK-1 [114] contributes to the inhibition of tumor cell migration, invasion, and survival [114], [115], [116], [117], [118].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [114]
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Metadata
- Authors
- Qiao, L., Xu, Z.-L., Zhao, T.-J., Ye, L.-H., & Zhang, X.-D.
- Affiliations
- Nankai University (CN)
- ORCID
- Qiao, Ling
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2008-09
- Volume
- 269
- Issue
- 1
- Pages
- 67-77
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2076704745
- Cited by
- 313
- References
- 43
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 19 · 2022: 22 · 2021: 29 · 2020: 19 · 2019: 17 · 2018: 16 · 2017: 19 · 2016: 20 · 2015: 26 · 2014: 27 · 2013: 25 · 2012: 20
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- DKK1, mesenchymal stem cells, breast cancer, MCF-7 cells, Wnt signaling, β-catenin, conditioned medium, tumor growth inhibition, secreted factors, paracrine signaling
- MeSH terms
- Animals, Breast Neoplasms, Cells, Cultured, Humans, Signal Transduction, Mice, SCID, Culture Media, Conditioned, Intercellular Signaling Peptides and Proteins, Cell Proliferation, Wnt Proteins, beta Catenin, Mice, Mesenchymal Stem Cells
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