Cargando…
Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review)
Head and neck squamous cell carcinoma (HNSCC) is one of the most widespread malignancies worldwide. p53, as a transcription factor, can play its role in tumor suppression by activating the expression of numerous target genes. However, p53 is one of the most commonly mutated genes, which frequently h...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394732/ https://www.ncbi.nlm.nih.gov/pubmed/37449494 http://dx.doi.org/10.3892/or.2023.8599 |
_version_ | 1785083436690571264 |
---|---|
author | Li, Minmin Sun, Dongyuan Song, Ning Chen, Xi Zhang, Xinyue Zheng, Wentian Yu, Yang Han, Chengbing |
author_facet | Li, Minmin Sun, Dongyuan Song, Ning Chen, Xi Zhang, Xinyue Zheng, Wentian Yu, Yang Han, Chengbing |
author_sort | Li, Minmin |
collection | PubMed |
description | Head and neck squamous cell carcinoma (HNSCC) is one of the most widespread malignancies worldwide. p53, as a transcription factor, can play its role in tumor suppression by activating the expression of numerous target genes. However, p53 is one of the most commonly mutated genes, which frequently harbors missense mutations. These missense mutations are nucleotide substitutions that result in the substitution of an amino acid in the DNA binding domain. Most p53 mutations in HNSCC are missense mutations and the mutation rate of p53 reaches 65–85%. p53 mutation not only inhibits the tumor suppressive function of p53 but also provides novel functions to facilitate tumor recurrence, called gain-of-function (GOF). The present study focused on the prevalence and clinical relevance of p53 mutations in HNSCC, and further described how mutant p53 accumulates. Moreover, mutant p53 in HNSCC can interact with proteins, RNA, and exosomes to exert effects on proliferation, migration, invasion, immunosuppression, and metabolism. Finally, several treatment strategies have been proposed to abolish the tumor-promoting function of mutant p53; these strategies include reactivation of mutant p53 into wild-type p53, induction of mutant p53 degradation, enhancement of the synthetic lethality of mutant p53, and treatment with immunotherapy. Due to the high frequency of p53 mutations in HNSCC, a further understanding of the mechanism of mutant p53 may provide potential applications for targeted therapy in patients with HNSCC. |
format | Online Article Text |
id | pubmed-10394732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-103947322023-08-03 Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review) Li, Minmin Sun, Dongyuan Song, Ning Chen, Xi Zhang, Xinyue Zheng, Wentian Yu, Yang Han, Chengbing Oncol Rep Review Head and neck squamous cell carcinoma (HNSCC) is one of the most widespread malignancies worldwide. p53, as a transcription factor, can play its role in tumor suppression by activating the expression of numerous target genes. However, p53 is one of the most commonly mutated genes, which frequently harbors missense mutations. These missense mutations are nucleotide substitutions that result in the substitution of an amino acid in the DNA binding domain. Most p53 mutations in HNSCC are missense mutations and the mutation rate of p53 reaches 65–85%. p53 mutation not only inhibits the tumor suppressive function of p53 but also provides novel functions to facilitate tumor recurrence, called gain-of-function (GOF). The present study focused on the prevalence and clinical relevance of p53 mutations in HNSCC, and further described how mutant p53 accumulates. Moreover, mutant p53 in HNSCC can interact with proteins, RNA, and exosomes to exert effects on proliferation, migration, invasion, immunosuppression, and metabolism. Finally, several treatment strategies have been proposed to abolish the tumor-promoting function of mutant p53; these strategies include reactivation of mutant p53 into wild-type p53, induction of mutant p53 degradation, enhancement of the synthetic lethality of mutant p53, and treatment with immunotherapy. Due to the high frequency of p53 mutations in HNSCC, a further understanding of the mechanism of mutant p53 may provide potential applications for targeted therapy in patients with HNSCC. D.A. Spandidos 2023-07-11 /pmc/articles/PMC10394732/ /pubmed/37449494 http://dx.doi.org/10.3892/or.2023.8599 Text en Copyright: © Li et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Review Li, Minmin Sun, Dongyuan Song, Ning Chen, Xi Zhang, Xinyue Zheng, Wentian Yu, Yang Han, Chengbing Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review) |
title | Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review) |
title_full | Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review) |
title_fullStr | Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review) |
title_full_unstemmed | Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review) |
title_short | Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review) |
title_sort | mutant p53 in head and neck squamous cell carcinoma: molecular mechanism of gain‑of‑function and targeting therapy (review) |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394732/ https://www.ncbi.nlm.nih.gov/pubmed/37449494 http://dx.doi.org/10.3892/or.2023.8599 |
work_keys_str_mv | AT liminmin mutantp53inheadandnecksquamouscellcarcinomamolecularmechanismofgainoffunctionandtargetingtherapyreview AT sundongyuan mutantp53inheadandnecksquamouscellcarcinomamolecularmechanismofgainoffunctionandtargetingtherapyreview AT songning mutantp53inheadandnecksquamouscellcarcinomamolecularmechanismofgainoffunctionandtargetingtherapyreview AT chenxi mutantp53inheadandnecksquamouscellcarcinomamolecularmechanismofgainoffunctionandtargetingtherapyreview AT zhangxinyue mutantp53inheadandnecksquamouscellcarcinomamolecularmechanismofgainoffunctionandtargetingtherapyreview AT zhengwentian mutantp53inheadandnecksquamouscellcarcinomamolecularmechanismofgainoffunctionandtargetingtherapyreview AT yuyang mutantp53inheadandnecksquamouscellcarcinomamolecularmechanismofgainoffunctionandtargetingtherapyreview AT hanchengbing mutantp53inheadandnecksquamouscellcarcinomamolecularmechanismofgainoffunctionandtargetingtherapyreview |