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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Mutant P53 in the formation and progression of the tumor microenvironment: Friend or foe
Elmira Roshani Asl1, Davoud Rostamzadeh2, Pascal H G Duijf3
1Department of Biochemistry, Saveh University of Medical Sciences, Saveh, Iran.
Abstract:
TP53 is the most frequently mutated gene in human cancer. It encodes the tumor suppressor protein p53, which suppresses tumorigenesis by acting as a critical transcription factor that can induce the expression of many genes controlling a plethora of fundamental cellular processes, including cell cycle progression, survival, apoptosis, and DNA repair. Missense mutations are the most frequent type of mutations in the TP53 gene. While these can have variable effects, they typically impair p53 function in a dominant-negative manner, thereby altering intra-cellular signaling pathways and promoting cancer development. Additionally, it is becoming increasingly apparent that p53 mutations also have non-cell autonomous effects that influence the tumor microenvironment (TME). The TME is a complex and heterogeneous milieu composed of both malignant and non-malignant cells, including cancer-associated fibroblasts (CAFs), adipocytes, pericytes, different immune cell types, such as tumor-associated macrophages (TAMs) and T and B lymphocytes, as well as lymphatic and blood vessels and extracellular matrix (ECM). Recently, a large body of evidence has demonstrated that various types of p53 mutations directly affect TME. They fine-tune the inflammatory TME and cell fate reprogramming, which affect cancer progression. Notably, re-educating the p53 signaling pathway in the TME may be an effective therapeutic strategy in combating cancer. Therefore, it is timely to here review the recent advances in our understanding of how TP53 mutations impact the fate of cancer cells by reshaping the TME.
Insights
TP53 mutations, common in cancer, impact tumor development by altering the tumor microenvironment (TME). Understanding these effects is key to developing new cancer therapies targeting the p53 signaling pathway within the TME.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- TP53 is the most frequently mutated gene in human cancers, encoding the critical tumor suppressor protein p53.
- TP53 mutations, particularly missense mutations, often impair p53 function in a dominant-negative manner, promoting cancer development.
- Emerging evidence highlights that p53 mutations exert non-cell autonomous effects, significantly influencing the tumor microenvironment (TME).
Purpose of the Study:
- To review recent advances in understanding how TP53 mutations impact cancer cell fate.
- To explore the mechanisms by which TP53 mutations reshape the tumor microenvironment (TME).
- To discuss the therapeutic potential of targeting the p53 signaling pathway within the TME.
Main Methods:
- Literature review of recent scientific publications.
- Analysis of studies investigating the role of TP53 mutations in cancer progression.
- Synthesis of data on the interaction between p53 mutations and the tumor microenvironment.
Main Results:
- TP53 mutations directly influence the TME, affecting inflammatory responses and cell fate reprogramming.
- Mutant p53 alters the composition and function of various TME components, including immune cells and fibroblasts.
- These TME modifications driven by TP53 mutations contribute to cancer progression and therapeutic resistance.
Conclusions:
- TP53 mutations play a crucial role in modulating the TME, impacting cancer progression.
- Targeting the p53 signaling pathway within the TME represents a promising therapeutic strategy for cancer treatment.
- Further research into the intricate interplay between TP53 mutations and the TME is warranted for novel cancer therapy development.
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