The Balance between Differentiation and Terminal Differentiation Maintains Oral Epithelial Homeostasis.
differentiation
epithelial integrity
epithelial transformation
genetic alterations
oral cancer
oral epithelium
terminal differentiation
therapy response biomarkers
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
13 Oct 2021
13 Oct 2021
Historique:
received:
30
08
2021
revised:
08
10
2021
accepted:
11
10
2021
entrez:
23
10
2021
pubmed:
24
10
2021
medline:
24
10
2021
Statut:
epublish
Résumé
The oral epithelium is one of the fastest repairing and continuously renewing tissues. Stem cell activation within the basal layer of the oral epithelium fuels the rapid proliferation of multipotent progenitors. Stem cells first undergo asymmetric cell division that requires tightly controlled and orchestrated differentiation networks to maintain the pool of stem cells while producing progenitors fated for differentiation. Rapidly expanding progenitors subsequently commit to advanced differentiation programs towards terminal differentiation, a process that regulates the structural integrity and homeostasis of the oral epithelium. Therefore, the balance between differentiation and terminal differentiation of stem cells and their progeny ensures progenitors commitment to terminal differentiation and prevents epithelial transformation and oral squamous cell carcinoma (OSCC). A recent comprehensive molecular characterization of OSCC revealed that a disruption of terminal differentiation factors is indeed a common OSCC event and is superior to oncogenic activation. Here, we discuss the role of differentiation and terminal differentiation in maintaining oral epithelial homeostasis and define terminal differentiation as a critical tumour suppressive mechanism. We further highlight factors with crucial terminal differentiation functions and detail the underlying consequences of their loss. Switching on terminal differentiation in differentiated progenitors is likely to represent an extremely promising novel avenue that may improve therapeutic interventions against OSCC.
Identifiants
pubmed: 34680271
pii: cancers13205123
doi: 10.3390/cancers13205123
pmc: PMC8534139
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
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