Journal
ARCHIVES OF ORAL BIOLOGY
Volume 128, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.archoralbio.2021.105164
Keywords
Matrix stiffness; Oral submucous fibrosis; Oral cancer; Hippo pathway; Cellular senescence
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Funding
- Science and Engineering Research Board (SERB), Department of Science and Technology, Government of India [EMR/2017/002792]
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This study elucidated the role of matrix stiffness in malignant transformation of oral submucous fibrosis, highlighting the involvement of YAP and TAZ in promoting cell migration, invasion, and epithelial-mesenchymal transition. It was found that increased matrix stiffness activates YAP and TAZ, serving as mechanical transducers to enhance tumor progression.
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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