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.

Abstract

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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