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Emerging role of cellular senescence in the pathogenesis of oral submucous fibrosis and its malignant transformation
Author(s) -
Sharma Mohit,
Hunter Keith D.,
Fonseca Felipe Paiva,
Radhakrishnan Raghu
Publication year - 2021
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.26805
Subject(s) - senescence , oral submucous fibrosis , malignant transformation , cancer research , fibrosis , pathogenesis , myofibroblast , dna damage , epithelial–mesenchymal transition , medicine , malignancy , cancer , biology , immunology , pathology , metastasis , dna , genetics
Senescence is a common denominator in wound healing, fibrosis, and cancer. Although, senescence is transiently antifibrotic, when prolonged, promotes fibrosis and malignant transformation. Eligible studies indexed in MEDLINE, Embase and Web of Science were searched to understand the role of cellular senescence in the pathogenesis of oral submucous fibrosis (OSF) and its malignant transformation. The senescence‐associated secretory phenotype (SASP) components like IL‐1, IL‐6, and GRO‐α induce double‐strand DNA breaks in keratinocytes and drive genetic instability. SASP derived from myofibroblasts induces epithelial–mesenchymal transition in OSF and facilitates cancer progression. The use of senolytics has been shown to eliminate senescent cells from the areas of fibrosis, thereby preventing malignancy. Naturally occurring agents such as apigenin and kaempferol inhibit SASP. Mechanistic insight into the emerging role of senescence in the pathogenesis of OSF and modalities to inhibit senescence‐associated antiapoptotic pathways as a supplementary therapy to prevent malignant transformation of OSF is underlined.