TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development.

Animals Carcinoma, Squamous Cell / genetics Cell Differentiation Chromatin / genetics Chromatin Assembly and Disassembly Epigenesis, Genetic Epithelial Cells / metabolism Gene Expression Regulation, Neoplastic Humans Transcription Factors / genetics Transcriptional Activation Tumor Suppressor Proteins / genetics
Basal cell Epigenetic reprogramming Histone modification Oncogene addiction SWI/SNF complex Ubiquitin–proteasome system

Journal

Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402

Informations de publication

Date de publication:
Nov 2020
Historique:
received: 25 10 2019
accepted: 24 04 2020
revised: 21 02 2020
pubmed: 25 5 2020
medline: 4 11 2020
entrez: 25 5 2020
Statut: ppublish

Résumé

Squamous cell carcinoma (SCC) is an aggressive malignancy that can originate from various organs. TP63 is a master regulator that plays an essential role in epidermal differentiation. It is also a lineage-dependent oncogene in SCC. ΔNp63α is the prominent isoform of TP63 expressed in epidermal cells and SCC, and overexpression promotes SCC development through a variety of mechanisms. Recently, ΔNp63α was highlighted to act as an epidermal-specific pioneer factor that binds closed chromatin and enhances chromatin accessibility at epidermal enhancers. ΔNp63α coordinates chromatin-remodeling enzymes to orchestrate the tissue-specific enhancer landscape and three-dimensional high-order architecture of chromatin. Moreover, ΔNp63α establishes squamous-like enhancer landscapes to drive oncogenic target expression during SCC development. Importantly, ΔNp63α acts as an upstream regulator of super enhancers to activate a number of oncogenic transcripts linked to poor prognosis in SCC. Mechanistically, ΔNp63α activates genes transcription through physically interacting with a number of epigenetic modulators to establish enhancers and enhance chromatin accessibility. In contrast, ΔNp63α also represses gene transcription via interacting with repressive epigenetic regulators. ΔNp63α expression is regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational levels. In this review, we summarize recent advances of p63 in epigenomic and transcriptional control, as well as the mechanistic regulation of p63.

Identifiants

DOI: 10.1007/s00018-020-03539-2 PMID: 32447427 PMC: PMC7588389
pubmed: 32447427
doi: 10.1007/s00018-020-03539-2
pii: 10.1007/s00018-020-03539-2
pmc: PMC7588389
doi:

Substances chimiques

Chromatin 0
TP63 protein, human 0
Transcription Factors 0
Tumor Suppressor Proteins 0

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

4325-4346

Subventions

Organisme : National Natural Science Foundation of China
ID : 81572667
Organisme : National Natural Science Foundation of China
ID : 81772902
Organisme : National Natural Science Foundation of China
ID : 81872278
Organisme : National Natural Science Foundation of China
ID : 81703131
Organisme : Natural Science Foundation of Hunan Province
ID : 2018JJ1040
Organisme : Hunan Provincial Science and Technology Department
ID : 2018SK2130
Organisme : Hunan Provincial Science and Technology Department
ID : 2018SK2131

Commentaires et corrections

Type : ErratumIn

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Auteurs

Mei Yi (M)

NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, 410078, Hunan, China.

Yixin Tan (Y)

Department of Dermatology, The Second Xiangya Hospital, The Central South University, Changsha, 410011, Hunan, China.

Li Wang (L)

Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.

Jing Cai (J)

NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, 410078, Hunan, China.

Xiaoling Li (X)

NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, 410078, Hunan, China.

Zhaoyang Zeng (Z)

NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, 410078, Hunan, China.

Wei Xiong (W)

NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, 410078, Hunan, China.

Guiyuan Li (G)

NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, 410078, Hunan, China.

Xiayu Li (X)

Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China. lixiayu@csu.edu.cn.

Pingqing Tan (P)

NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China. tanpingqing@hnszlyy.com.
Department of Head and Neck Surgery, Hunan Provincial Cancer Hospital and Cancer Hospital Affiliated to Xiangya Medical School, Central South University, Changsha, 410013, Hunan, China. tanpingqing@hnszlyy.com.

Bo Xiang (B)

NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China. xiangbolin@csu.edu.cn.
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China. xiangbolin@csu.edu.cn.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, 410078, Hunan, China. xiangbolin@csu.edu.cn.
ORCID: 0000-0003-2641-5434

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › TP63 links chromatin remodeling and enhancer...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Tumeurs épidermoïdes › Carcinome épidermoïde › TP63 links chromatin remodeling and enhancer...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › TP63 links chromatin remodeling and enhancer...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › TP63 links chromatin remodeling and enhancer...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Assemblage et désassemblage de la chromatine › TP63 links chromatin remodeling and enhancer...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › TP63 links chromatin remodeling and enhancer...
questionsmedicales.fr › Cellules › Cellules épithéliales › TP63 links chromatin remodeling and enhancer...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › TP63 links chromatin remodeling and enhancer...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › TP63 links chromatin remodeling and enhancer...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › TP63 links chromatin remodeling and enhancer...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Activation de la transcription › TP63 links chromatin remodeling and enhancer...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › TP63 links chromatin remodeling and enhancer...