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Changes in p53 expression in mouse fibroblasts can modify motility and extracellular matrix organization
A Alexandrova1, A Ivanov, P Chumakov
1Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia.
Oncogene
|December 29, 2000
Summary
p53 expression alters cell shape and cytoskeleton, reducing cell area and focal contacts. Despite increased edge activity, p53-expressing cells show reduced migration, impacting wound healing.
Area of Science:
- Cell Biology
- Molecular Biology
- Biophysics
Background:
- The tumor suppressor protein p53 plays a critical role in cellular responses to stress.
- Understanding p53's impact on cell morphology and motility is crucial for cancer research and therapeutic development.
Purpose of the Study:
- To investigate how p53 expression affects the morphology and motility of mouse fibroblasts.
- To elucidate the specific cellular changes induced by p53, including extracellular matrix interactions and cytoskeletal organization.
Main Methods:
- Utilized tetracycline-regulated expression of exogenous human p53 in p53-null mouse fibroblasts.
- Employed techniques such as videomicroscopy, wound healing assays, and analysis of extracellular matrix components (fibronectin) and focal adhesions.
Main Results:
- p53 induction led to decreased fibronectin, reduced focal contacts, smaller cell areas, and altered actin cytoskeleton.
- While p53 expression increased lamellar activity, it resulted in decreased cell migration distance and slower wound filling.
- p53 mutants (His175, Gln22/Ser23) did not induce these morphological or motility changes.
Conclusions:
- p53 expression significantly alters fibroblast morphology and reduces cell motility, despite enhanced lamellar activity.
- These findings suggest a complex role for p53 in regulating cell migration dynamics, potentially through cytoskeletal and extracellular matrix interactions.