ArticleBMC cancer2011
SFRP1 reduction results in an increased sensitivity to TGF-β signaling.
Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Despicable role of epithelial-mesenchymal transition in breast cancer metastasis: ExhibitingCancer pathogenesis and therapy · 2025Review
- Regulation of the Epithelial to Mesenchymal Transition in Osteosarcoma.Biomolecules · 2023Review
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- Dynamic EMT: a multi-tool for tumor progression.The EMBO journal · 2021Review
- Intercellular coupling between peripheral circadian oscillators by TGF-β signaling.Science advances · 2021Article
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- Epigenetics ofCancers · 2020Review
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- Gene expression signature of atypical breast hyperplasia and regulation by SFRP1.Breast cancer research : BCR · 2019Article
- Perspectives of small molecule inhibitors of activin receptor‑like kinase in anti‑tumor treatment and stem cell differentiation (Review).Molecular medicine reports · 2019Review
- New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer.Nature reviews. Molecular cell biology · 2019Review
- Spontaneous generation of a novel foetal human retinal pigment epithelium (RPE) cell line available for investigation on phagocytosis and morphogenesis.Cell proliferation · 2017Article
- Regulation of early growth response 2 expression by secreted frizzled related protein 1.BMC cancer · 2017Article
- The role of TGF-β and its crosstalk with RAC1/RAC1b signaling in breast and pancreas carcinoma.Cell communication and signaling : CCS · 2017Review
- Grhl2 reduces invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer.Oncogenesis · 2017Article
- Downregulation of HP1α suppresses proliferation of cholangiocarcinoma by restoring SFRP1 expression.Oncotarget · 2016Article
- Article
- Influence of secreted frizzled receptor protein 1 (SFRP1) on neoadjuvant chemotherapy in triple negative breast cancer does not rely on WNT signaling.Molecular cancer · 2014Article
- Secreted frizzled related protein 1 modulates taxane resistance of human lung adenocarcinoma.Molecular medicine (Cambridge, Mass.) · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTransforming growth factor (TGF)-β plays a dual role during mammary gland development and tumorigenesis and has been shown to stimulate epithelial-mesenchymal transition (EMT) as well as cellular migration. The Wnt/β-catenin pathway is also implicated in EMT and inappropriate activation of the Wnt/β-catenin signaling pathway leads to the development of several human cancers, including breast cancer. Secreted frizzled-related protein 1 (SFRP1) antagonizes this pathway and loss of SFRP1 expression is frequently observed in breast tumors and breast cancer cell lines. We previously showed that when SFRP1 is knocked down in immortalized non-malignant mammary epithelial cells, the cells (TERT-siSFRP1) acquire characteristics associated with breast tumor initiating cells. The phenotypic and genotypic changes that occur in response to SFRP1 loss are consistent with EMT, including a substantial increase in the expression of ZEB2. Considering that ZEB2 has been shown to interact with mediators of TGF-β signaling, we sought to determine whether TGF-β signaling is altered in TERT-siSFRP1 cells.
methodsLuciferase reporter assays and real-time PCR analysis were employed to measure TGF-β transcriptional targets. Western blot analysis was used to evaluate TGF-β-mediated ERK1/2 phosphorylation. Migration chamber assays were utilized to quantify cellular migration. TERT-siSFRP1 cells were transfected with Stealth RNAi™ siRNA in order to knock-down the expression of ZEB2.
resultsTERT-siSFRP1 cells exhibit a significant increase in both TGF-β-mediated luciferase activity as well as TGF-β transcriptional targets, including Integrin β3 and PAI-1. Phosphorylation of ERK1/2 is increased in TERT-siSFRP1 cells in response to enhanced TGF-β signaling. Furthermore, when the TGF-β pathway is blocked with a TGF-βR antagonist (LY364947), cellular migration is significantly hindered. Finally, we found that when ZEB2 is knocked-down, there is a significant reduction in the expression of exogeneous and endogenous TGF-β transcriptional targets and cellular migration is impeded.
conclusionsWe demonstrate that down-regulation of SFRP1 renders mammary epithelial cells more sensitive to TGF-β signaling which can be partially ameliorated by blocking the expression of ZEB2.
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