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Updated: Nov 28, 2025

Analysis of Cell Migration within a Three-dimensional Collagen Matrix
Published on: October 5, 2014
Overexpression of DDR1 Promotes Migration, Invasion, Though EMT-Related Molecule Expression and COL4A1/DDR1/MMP-2
Xin Xie1, Hongchao He1, Ning Zhang1
1Department of Urology, Ruijin Hospital, 56694Shanghai Jiaotong University School of Medicine, Shanghai, China.
Purpose:
Discoidin domain receptor 1 (DDR1) belongs to a novel class of receptor tyrosine kinases. Previous evidence indicates that DDR1 overexpression promotes the aggressive growth of bladder cancer (BC) cells. This study aimed to investigate the molecular mechanisms by which DDR1 influences BC.
Methods:
DDR1 was transfected into human BC RT4 cells. DDR1, COL4A1, and MMP-2 expression in 30 BC tissues and paired adjacent tissues were examined by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Transwell assays were conducted to determine cell migration and invasion. RT-PCR and western blot (WB) were also used to measure the DDR1, COL4A1, MMP-2, and EMT-related gene (ZEB1 and SLUG) expression in RT4 cells after DDR1 overexpression.
Results:
COL4A1 and MMP-2 interacted with DDR1 in the PPI network. RT-PCR and immunohistochemistry results showed that both mRNA and protein levels of DDR1 and COL4A1 were significantly increased in BC tissue, while the expression of MMP-2 was increased only at the mRNA level (P < 0.05). Overexpression of DDR1 in RT4 cells significantly promoted their migratory and invasive capabilities in vitro (P < 0.05). Moreover, overexpression of DDR1 in RT4 cells increased the mRNA and protein expression of ZEB1, SLUG, COL4A1, and MMP-2 (P < 0.01). DDR1-mediated migration and invasion of RT4 cells were reversed after COL4A1-siRNA treatment.
Conclusion:
DDR1 may be a potential therapeutic target in BC patients.
Insights
Discoidin domain receptor 1 (DDR1) overexpression promotes bladder cancer (BC) cell growth and invasion by upregulating collagen type IV alpha 1 chain (COL4A1) and matrix metalloproteinase-2 (MMP-2). Targeting DDR1 may offer a new therapeutic strategy for BC patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase implicated in aggressive bladder cancer (BC) growth.
- Understanding the molecular mechanisms of DDR1 in BC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the molecular mechanisms by which DDR1 influences bladder cancer progression.
- To explore the role of DDR1 in BC cell migration and invasion.
Main Methods:
- DDR1 was overexpressed in human BC RT4 cells.
- Gene and protein expression of DDR1, COL4A1, MMP-2, ZEB1, and SLUG were analyzed using RT-PCR and Western blot.
- Cell migration and invasion assays (Transwell) were performed.
- siRNA targeting COL4A1 was used to assess its role in DDR1-mediated effects.
Main Results:
- DDR1 and COL4A1 mRNA and protein levels were significantly elevated in BC tissues compared to adjacent tissues.
- MMP-2 mRNA levels were increased in BC tissues.
- DDR1 overexpression in RT4 cells enhanced cell migration and invasion.
- DDR1 overexpression led to increased expression of ZEB1, SLUG, COL4A1, and MMP-2.
- COL4A1 knockdown reversed DDR1-induced cell migration and invasion.
Conclusions:
- DDR1 plays a significant role in promoting bladder cancer cell migration and invasion.
- DDR1, COL4A1, and MMP-2 are potential biomarkers and therapeutic targets for bladder cancer.
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