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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Understanding p53: new insights into tumor suppression
Keiko Kawauchi1, Steven John Wolf
1Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-minamimachi, Kobe, Hyogo 650-0047, Japan.
Abstract:
p53 (aka TP53) is a powerful tumor suppressor, and oncogenic transformation is induced when the ability of p53 to suppress tumorigenesis is compromised. p53 not only prevents tumorigenesis, but also tumor progression, that is, local invasion and distant metastasis. Recently, we showed that cytoplasmic p53 prevents RAS-driven invasion via alteration of actin cytoskeleton remodeling. This follows modulation of mitochondrial integrity. The transcriptional activity of p53 has been restored using small molecules; however, their success as cancer therapies is largely dependent on the status of downstream targets of p53. It is therefore important to elucidate the role of these downstream targets in p53 regulated tumor progression. With the recently described mechanism of tumor suppression highlighting a role of p53's downstream targets in the regulation of actin cytoskeleton dynamics and lamellipodia formation, we suggest that potential therapeutic targets may be revealed within this mechanism that can be exploited in anticancer therapy.
Insights
The tumor suppressor p53 (TP53) prevents cancer progression. Cytoplasmic p53 inhibits invasion by altering actin remodeling, suggesting new therapeutic targets for cancer therapy.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- p53 (TP53) is a critical tumor suppressor protein that inhibits oncogenic transformation, tumor progression, invasion, and metastasis.
- Compromised p53 function is linked to cancer development.
- Recent findings indicate a role for cytoplasmic p53 in preventing invasion via actin cytoskeleton remodeling and mitochondrial integrity modulation.
Purpose of the Study:
- To elucidate the role of p53's downstream targets in regulating tumor progression.
- To identify potential therapeutic targets within the p53-regulated mechanism of tumor suppression.
Main Methods:
- Investigated the mechanism by which cytoplasmic p53 suppresses RAS-driven invasion.
- Focused on the modulation of actin cytoskeleton dynamics and lamellipodia formation.
- Examined the role of p53's downstream targets in these processes.
Main Results:
- Demonstrated that cytoplasmic p53 prevents RAS-driven invasion.
- Showed that this process involves the alteration of actin cytoskeleton remodeling.
- Highlighted the involvement of mitochondrial integrity modulation.
Conclusions:
- p53's downstream targets play a crucial role in regulating actin cytoskeleton dynamics and lamellipodia formation.
- The identified mechanism of tumor suppression by p53 offers potential therapeutic targets for anticancer strategies.
- Restoring p53 transcriptional activity is a therapeutic approach, but its efficacy depends on downstream target status.
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