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Review
. 2021 Oct 13;13(20):5123.
doi: 10.3390/cancers13205123.

The Balance between Differentiation and Terminal Differentiation Maintains Oral Epithelial Homeostasis

Yuchen Bai  1 , Jarryd Boath  1 , Gabrielle R White  1 , Uluvitike G I U Kariyawasam  1 , Camile S Farah  1   2 , Charbel Darido  1   3
Affiliations
Review

The Balance between Differentiation and Terminal Differentiation Maintains Oral Epithelial Homeostasis

Yuchen Bai et al. Cancers (Basel). .

Abstract

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.

Keywords: differentiation; epithelial integrity; epithelial transformation; genetic alterations; oral cancer; oral epithelium; terminal differentiation; therapy response biomarkers.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation (original figure) of the oral layers in homeostasis (left) with a highlight of the basal layer depicting major players in epithelial differentiation (middle) and those regulating terminal differentiation in the superficial layer (right).
See this image and copyright information in PMC

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