Role of Yes-associated protein and transcriptional coactivator with PDZ-binding motif in the malignant transformation of oral submucous fibrosis

Sharma M 1 , Hunter KD 2 , Fonseca FP 3 , Shetty SS 4 , Radhakrishnan R 5

Affiliations 

  • 1 Department of Oral Pathology, Sudha Rustagi College of Dental Sciences and Research, Faridabad, India
  • 2 Academic Unit of Oral and Maxillofacial Medicine and Pathology, School of Clinical Dentistry, University of Sheffield, S10 2TA, United Kingdom
  • 3 Department of Oral Pathology and Surgery, School of Dentistry, Universidade Federal De Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil
  • 4 Department of Oral Pathology, Faculty of Dentistry, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, India
  • 5 Department of Oral Pathology, Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal, 576104, India. Electronic address: raghu.ar@manipal.edu
Arch Oral Biol, 2021 Aug;128:105164.
PMID: 34044344 DOI: 10.1016/j.archoralbio.2021.105164

Abstract

OBJECTIVE(S): The objective of the present manuscript is to elucidate the role of matrix stiffness in the malignant transformation of oral submucous fibrosis.

DESIGN: The role of matrix stiffness in several cancers including oral cancer was reviewed with a tailored search strategy using relevant keywords as per the Medline format. The role of molecular mediators, Yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) was weighed in the context of OSF along two distinct pathways.

RESULTS: Increased matrix stiffness activates the transcriptional coactivators, YAP and TAZ shuttling between the nucleus and cytoplasm. YAP and TAZ, serve as mechanical transducers in promoting cell migration, invasion and epithelial-mesenchymal transition (EMT). The hypoxic microenvironment in the advanced stage of OSF promotes the migratory phenotype through mechanical memory.

CONCLUSIONS: Reprogramming of a stiff matrix has the potential to restore the Hippo-YAP/TAZ tumor suppressor pathway and reverse fibrosis-associated tumor development.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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