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Related Experiment Videos

Integrin alpha6 cleavage: a novel modification to modulate cell migration.

Sangita C Pawar1, Manolis C Demetriou, Raymond B Nagle

  • 1Dept. of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA.

Experimental Cell Research
|February 17, 2007
PubMed
Summary
This summary is machine-generated.

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Cleavage of integrin alpha6 by urokinase-type Plasminogen Activator (uPA) promotes prostate cancer cell invasion and migration. This uPA-mediated cleavage enhances tumor cell movement on laminin substrates.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Integrins are crucial for cell adhesion and migration.
  • A cleaved form of integrin alpha6 (alpha6p) is present in invasive prostate cancer but not normal tissue.
  • Urokinase-type Plasminogen Activator (uPA) produces alpha6p independently of plasmin.

Purpose of the Study:

  • To identify the specific amino acid residues involved in integrin alpha6 cleavage.
  • To investigate the role of integrin alpha6 cleavage in prostate cancer cell invasion and migration.

Main Methods:

  • Site-directed mutagenesis to identify cleavage residues (R594, R595) in integrin alpha6.
  • Stable transfection of prostate cancer cells (PC3N) to express wild-type (PC3N-alpha6-WT) or non-cleavable (PC3N-alpha6-RR) integrin alpha6.

Related Experiment Videos

  • Invasion assays using laminin-coated filters and migration assays on laminin substrates.
  • Treatment with plasminogen activator inhibitor-1 (PAI-1) and aprotinin to assess the role of uPA and plasmin.

    • Main Results:

    • PC3N-alpha6-WT cells showed a threefold increase in invasion compared to PC3N-alpha6-RR cells.
    • PAI-1 reduced invasion of PC3N-alpha6-WT cells by 42% on laminin 332, while aprotinin had no significant effect.
    • Linear cell migration assays revealed increased alpha6p production in PC3N-alpha6-WT cells and significantly higher migration on laminin 111 (32% vs 5%).

    Conclusions:

    • The uPA-mediated cleavage of the integrin alpha6 extracellular domain is essential for prostate tumor cell invasion and migration.
    • Specific residues R594 and R595 in the integrin alpha6 stalk region are critical for this cleavage.
    • Targeting this cleavage mechanism may offer therapeutic strategies for prostate cancer treatment.