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SDCBP Cooperates With YBX1 to Promote ESCC Metastasis by Forming a Positive Feedback Loop With Wnt-β-Catenin
Ruijuan Du1,2, Bo Bian3, Manyu Luo1
1Zhang Zhongjing School of Chinese Medicine, Nanyang Institute of Technology, Nanyang, China.
Syndecan binding protein (SDCBP) promotes esophageal squamous cell carcinoma (ESCC) metastasis by driving epithelial-mesenchymal transition (EMT) and activating the Wnt-β-catenin pathway. Targeting SDCBP offers a potential therapeutic strategy for ESCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis
Background:
- Syndecan binding protein (SDCBP) is upregulated in esophageal squamous cell carcinoma (ESCC) and linked to poor prognosis.
- SDCBP promotes tumor proliferation and formation, suggesting its potential as an ESCC therapeutic target.
- The role of SDCBP in epithelial-mesenchymal transition (EMT) and ESCC metastasis remains largely unexplored.
Purpose of the Study:
- To investigate the role of SDCBP in ESCC cell epithelial-mesenchymal transition (EMT) and metastasis.
- To elucidate the molecular mechanisms underlying SDCBP-mediated ESCC metastasis, including its interaction with the Wnt-β-catenin pathway and Y-box binding protein 1 (YBX1).
- To explore the regulatory relationship between SDCBP and the Wnt-β-catenin pathway in ESCC.
Main Methods:
- In vitro and in vivo assays were used to assess SDCBP's effect on ESCC cell EMT and metastasis.
- Western blotting and immunofluorescence were employed to analyze protein expression and localization, particularly for β-catenin.
- Co-immunoprecipitation assays were performed to investigate the interaction between SDCBP and YBX1.
- Gene expression analysis was conducted to evaluate the impact on Wnt-β-catenin pathway target genes.
Main Results:
- SDCBP significantly promoted EMT in ESCC cells and facilitated metastasis both in vitro and in vivo.
- SDCBP influenced Wnt-β-catenin pathway activation, regulating β-catenin expression and nuclear localization.
- SDCBP interacted with YBX1, and upregulated YBX1 mediated SDCBP-driven ESCC cell migration and invasion.
- A positive feedback loop was identified where SDCBP is transcriptionally regulated by the Wnt-β-catenin pathway.
Conclusions:
- SDCBP plays a crucial role in promoting ESCC metastasis by inducing EMT and activating the Wnt-β-catenin pathway.
- The SDCBP-YBX1-Wnt-β-catenin axis is a key regulator of ESCC migration and invasion.
- The positive feedback loop between SDCBP and Wnt-β-catenin pathway provides a deeper understanding of ESCC progression.
- SDCBP represents a promising therapeutic target for inhibiting ESCC metastasis.
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