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Updated: Jun 6, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
SOSTDC1 differentially modulates Smad and beta-catenin activation and is down-regulated in breast cancer
Kathryn A Clausen1, Kimberly R Blish, Charles E Birse
1Department of Cancer Biology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. kclausen@wfubmc.edu
Abstract:
Sclerostin domain containing 1 (SOSTDC1) protein regulates processes from development to cancer by modulating activity of bone morphogenetic protein (BMP) and wingless/int (Wnt) signaling pathways. As dysregulation of both BMP and Wnt signaling has been observed in breast cancer, we investigated whether disruption of SOSTDC1 signaling occurs in breast cancer. SOSTDC1 mRNA expression levels in breast tissue were examined using a dot blot. Affymetrix microarray data on SOSTDC1 levels were correlated with breast cancer patient survival using Kaplan-Meier plots. Correlations between SOSTDC1 protein levels and clinical parameters were assessed by immunohistochemistry of a breast cancer tissue microarray. SOSTDC1 secretion and BMP and Wnt signaling were investigated using immunoblotting. We found that SOSTDC1 is expressed in normal breast tissue and this expression is reduced in breast cancer. High levels of SOSTDC1 mRNA correlated with increased patient survival; conversely, SOSTDC1 protein levels decreased as tumor size and disease stage increased. Treatment of breast cancer cells with recombinant SOSTDC1 or Wise, a SOSTDC1 orthologue, demonstrated that SOSTDC1 selectively blocks BMP-7-induced Smad phosphorylation without diminishing BMP-2 or Wnt3a-induced signaling. In conclusion, SOSTDC1 mRNA and protein are reduced in breast cancer. High SOSTDC1 mRNA levels correlate with increased distant metastasis-free survival in breast cancer patients. SOSTDC1 differentially affects Wnt3a, BMP-2, and BMP-7 signaling in breast cancer cells. These results identify SOSTDC1 as a clinically important extracellular regulator of multiple signaling pathways in breast cancer.
Insights
Sclerostin domain containing 1 (SOSTDC1) is reduced in breast cancer, with lower SOSTDC1 linked to poorer survival. This protein selectively impacts BMP and Wnt signaling pathways, suggesting its potential as a therapeutic target.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- Sclerostin domain containing 1 (SOSTDC1) protein influences development and cancer by modulating bone morphogenetic protein (BMP) and wingless/int (Wnt) signaling.
- Dysregulation of BMP and Wnt signaling is implicated in breast cancer progression.
Purpose of the Study:
- To investigate the role and disruption of SOSTDC1 signaling in breast cancer.
- To determine the correlation between SOSTDC1 expression levels and breast cancer patient outcomes.
Main Methods:
- Dot blot analysis of SOSTDC1 mRNA expression in breast tissue.
- Correlation of Affymetrix microarray data with patient survival using Kaplan-Meier plots.
- Immunohistochemistry to assess SOSTDC1 protein levels and clinical parameters.
Main Results:
- SOSTDC1 expression is reduced in breast cancer compared to normal tissue.
- Higher SOSTDC1 mRNA levels correlate with improved patient survival and increased distant metastasis-free survival.
- SOSTDC1 protein levels decrease with increasing tumor size and disease stage.
- SOSTDC1 selectively inhibits BMP-7-induced Smad phosphorylation, without affecting BMP-2 or Wnt3a signaling.
Conclusions:
- SOSTDC1 is downregulated in breast cancer, and its reduced expression is associated with adverse clinical outcomes.
- SOSTDC1 acts as a differential regulator of BMP and Wnt signaling pathways in breast cancer cells.
- SOSTDC1 represents a clinically significant extracellular regulator in breast cancer, potentially offering therapeutic avenues.
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