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Mutant P53 in the formation and progression of the tumor microenvironment: Friend or foe
被引:19
作者:
Asl, Elmira Roshani
[1
]
Rostamzadeh, Davoud
[2
,3
]
Duijf, Pascal H. G.
[4
,5
,6
,7
,8
,9
]
Mafi, Sahar
[2
,3
]
Mansoori, Behnaz
[10
]
Barati, Shirin
[11
]
Cho, William C.
[12
]
Mansoori, Behzad
[13
]
机构:
[1] Saveh Univ Med Sci, Dept Biochem, Saveh, Iran
[2] Yasuj Univ Med Sci, Dept Clin Biochem, Yasuj, Iran
[3] Yasuj Univ Med Sci, Med Plants Res Ctr, Yasuj, Iran
[4] Queensland Univ Technol, Fac Hlth, Sch Biomed Sci, Brisbane, Qld, Australia
[5] Queensland Univ Technol, Ctr Genom & Personalised Hlth, Brisbane, Qld, Australia
[6] Queensland Univ Technol, Ctr Data Sci, Brisbane, Qld, Australia
[7] Queensland Univ Technol, Canc & Aging Res Program, Brisbane, Qld, Australia
[8] Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway
[9] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway
[10] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran
[11] Saveh Univ Med Sci, Dept Anat, Saveh, Iran
[12] Queen Elizabeth Hosp, Dept Clin Oncol, Hong Kong, Peoples R China
[13] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, Philadelphia, PA 19104 USA
来源:
关键词:
Cancer;
TP53;
Mutated p53;
Tumor microenvironment;
Cancer-associated fibroblasts;
Extracellular matrix;
EPITHELIAL-MESENCHYMAL TRANSITION;
GAIN-OF-FUNCTION;
CANCER-ASSOCIATED FIBROBLASTS;
REGULATORY T-CELLS;
SUPPRESSOR GENE;
EXTRACELLULAR-MATRIX;
COLORECTAL-CANCER;
OXIDATIVE STRESS;
TP53;
MUTATIONS;
STROMAL CELLS;
D O I:
10.1016/j.lfs.2022.121361
中图分类号:
R-3 [医学研究方法];
R3 [基础医学];
学科分类号:
1001 ;
摘要:
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 intracellular 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 tumorassociated 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.
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页数:13
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