Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signalling

Qiao, Ling; Xu, Zhi-li; Zhao, Tie-jun; Ye, Li-hong; Zhang, Xiao-dong

doi:10.1016/j.canlet.2008.04.032

Cited by 313Wnt/β-catenin signaling in development and cancerMesenchymal stem cell researchCancer Cells and Metastasis

Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signalling

Qiao, Ling, Xu, Zhi-li, Zhao, Tie-jun, Ye, Li-hong, Zhang, Xiao-dong·2008·Cancer Letters

DOI 10.1016/j.canlet.2008.04.032

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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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Disruption of PI3K/AKT via upregulation of PTEN and of WNT/β-catenin signaling by MSC-secreted DKK-1 contributes to inhibition of tumor cell migration, invasion, and survival.
“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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“…of the cancer-associated signaling pathways, such as PI3K/AKT [107,113], via upregulation of PTEN, and of WNT/ b - 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 [114–118].”
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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)
DOI: 10.1016/j.canlet.2008.04.032
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cancer Letters (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
Health Sciences › Medicine › Genetics › 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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Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signalling

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