Related Experiment Video
Updated: Apr 23, 2026
Using In Vivo and Tissue and Cell Explant Approaches to Study the Morphogenesis and Pathogenesis of the Embryonic and Perinatal Aorta
Published on: September 12, 2017
p53 Down regulates PDGF-induced formation of circular dorsal ruffles in rat aortic smooth muscle cells
Laura J Payne1, Robert L Eves1, Lilly Jia1
1Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Abstract:
The tumor suppressor, p53, negatively regulates cell migration and invasion in addition to its role in apoptosis, cell cycle regulation and senescence. Here, we study the roles of p53 in PDGF-induced circular dorsal ruffle (CDR) formation in rat aortic smooth muscle (RASM) cells. In primary and immortalized RASM cells, up-regulation of p53 expression or increase in activity with doxorubicin inhibits CDR formation. In contrast, shRNA-knockdown of p53 or inhibition of its activity with pifithrin α promotes CDR formation. p53 acts by up-regulating PTEN expression, which antagonizes Rac and Cdc42 activation. Both lipid and protein phosphatase activities of PTEN are required for maximal suppression of CDR, but the lipid activity clearly plays the dominant role. N-WASP, the downstream effector of Cdc42, is the major positive contributor to CDR formation in RASM, and is an indirect target of p53. The Rac effector, WAVE2, appears to also play a minor role, while WAVE1 has no significant effect in CDR formation. In sum, we propose that p53 suppresses PDGF-induced CDR formation in RASM cells by upregulating PTEN leading mainly to the inhibition of the Cdc42-N-WASP pathway.
Insights
The tumor suppressor p53 inhibits cell migration by upregulating PTEN, which blocks the Cdc42-N-WASP pathway. This finding reveals a new mechanism for p53
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- The tumor suppressor p53 is known to regulate apoptosis, cell cycle, and senescence.
- p53 also plays a role in negatively regulating cell migration and invasion.
- Circular dorsal ruffle (CDR) formation is a cellular process linked to migration and invasion.
Purpose of the Study:
- To investigate the role of p53 in Platelet-Derived Growth Factor (PDGF)-induced CDR formation in rat aortic smooth muscle (RASM) cells.
- To elucidate the molecular mechanisms by which p53 influences CDR formation.
Main Methods:
- Studied p53's effect on CDR formation in primary and immortalized RASM cells.
- Manipulated p53 expression and activity using doxorubicin, shRNA-knockdown, and pifithrin α.
- Assessed PTEN expression and its phosphatase activities (lipid and protein).
- Investigated the roles of downstream effectors like N-WASP, WAVE1, and WAVE2.
Main Results:
- Increased p53 expression or activity inhibited PDGF-induced CDR formation.
- p53 knockdown or inhibition promoted CDR formation.
- p53 upregulates PTEN expression, which antagonizes Rac and Cdc42 activation, with lipid phosphatase activity being dominant.
- The Cdc42 effector N-WASP is a major positive regulator of CDR and an indirect target of p53; Rac effector WAVE2 plays a minor role.
Conclusions:
- p53 suppresses PDGF-induced CDR formation in RASM cells.
- This suppression is mediated by p53-induced upregulation of PTEN, primarily inhibiting the Cdc42-N-WASP pathway.
- Identifies a novel mechanism for p53's tumor-suppressive function related to cell migration.
More Related Videos
08:28Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
Published on: February 15, 2022
11:38Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
Related Concept Videos
02:23Abnormal Proliferation
01:24Regulation of Angiogenesis and Blood Supply
01:23Negative Regulator Molecules