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Fulltext Signaling pathways promoting epithelial mesenchymal transition in oral submucous fibrosis and oral squamous cell carcinoma

Shetty SS, Sharma M, Fonseca FP, Jayaram P, Tanwar AS, Kabekkodu SP, et al.

Jpn Dent Sci Rev, 2020 Nov;56(1):97-108.
PMID: 32874377 DOI: 10.1016/j.jdsr.2020.07.002

Epithelial-mesenchymal transition (EMT) is a critical process that occurs during the embryonic development, wound healing, organ fibrosis and the onset of malignancy. Emerging evidence suggests that the EMT is involved in the invasion and metastasis of cancers. The inflammatory reaction antecedent to fibrosis in the onset of oral submucous fibrosis (OSF) and the role of EMT in its malignant transformation indicates a hitherto unexplored involvement of EMT. This review focuses on the role of EMT markers which are regulators of the EMT mediated complex network of molecular mechanisms involved in the pathogenesis of OSF and OSCC. Further the gene enrichment analysis and pathway analysis supports the association of the upregulated and downregulated genes in various EMT regulating pathways.
Role of Yes-associated protein and transcriptional coactivator with PDZ-binding motif in the malignant transformation of oral submucous fibrosis

Sharma M, Hunter KD, Fonseca FP, Shetty SS, Radhakrishnan R

Arch Oral Biol, 2021 Aug;128:105164.
PMID: 34044344 DOI: 10.1016/j.archoralbio.2021.105164

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.

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