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Reduced expression of (alpha)5(beta)1 integrin prevents spreading-dependent cell proliferation
G Davey1, M Buzzai, R K Assoian
1Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6084, USA.
Journal of Cell Science
|November 27, 1999
Summary
Reducing alpha5 integrin (α5β1) in NRK cells impairs cell spreading and proliferation. Restoring spreading on collagen did not rescue proliferation, indicating cytoskeletal organization is key for integrin-mediated cell growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cell adhesion initiates integrin signaling and cytoskeleton organization (cell spreading).
- The relationship between cell spreading, cytoskeleton organization, and cell proliferation requires further investigation.
Purpose of the Study:
- To investigate the link between alpha5beta1 integrin, cell spreading, and cell proliferation in NRK fibroblasts.
- To determine if restoring cell spreading can rescue impaired proliferation.
Main Methods:
- NRK fibroblasts were transfected with antisense cDNA to selectively reduce alpha5beta1 integrin expression.
- Cell spreading, stress fiber formation, cortical actin, and proliferation rates were analyzed.
- Antisense cells were plated on collagen to assess rescue of cell spreading and proliferation.
Main Results:
- Alpha5-antisense NRK cells exhibited reduced cell spreading, poorly defined stress fibers, and increased cortical actin.
- These cells showed anchorage-dependent but very slow proliferation with an impaired response to mitogens.
- Plating on collagen restored cell spreading and stress fibers but failed to rescue proliferation.
Conclusions:
- Cell spreading can be uncoupled from cell proliferation.
- Cytoskeletal organization is crucial for mediating the proliferative effects of alpha5beta1 integrin.
- Reduced alpha5beta1 integrin expression alone does not induce anchorage-independent growth in non-transformed cells.