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  1. Article: The interplay of EMT and stemness driving malignant transformation of Oral Submucous Fibrosis.

    Shetty, Smitha Sammith / Sharma, Mohit / Padam, Kanaka Sai Ram / Kudva, Adarsh / Patel, Pratik / Radhakrishnan, Raghu

    Journal of oral biology and craniofacial research

    2024  Volume 14, Issue 1, Page(s) 63–71

    Abstract: Background: Oral submucous fibrosis (OSF) is a persistent oral mucosal condition that carries an elevated risk of undergoing malignant transformation. Our objective was to elucidate the involvement of epithelial-to-mesenchymal transition (EMT) in OSF ... ...

    Abstract Background: Oral submucous fibrosis (OSF) is a persistent oral mucosal condition that carries an elevated risk of undergoing malignant transformation. Our objective was to elucidate the involvement of epithelial-to-mesenchymal transition (EMT) in OSF and its progression to malignancy by studying a panel of EMT markers, thereby understanding the molecular mechanisms.
    Methods: An immunohistochemical analysis was done to detect the presence of E-cadherin, N-cadherin, pan-cytokeratin (PanCK), vimentin, α-SMA (alpha-smooth muscle actin), and CD44 in a total of 100 tissue samples. These samples comprised 40 cases of OSF, 20 cases of oral squamous cell carcinoma associated with OSF (OSFSCC), and 40 cases of oral squamous cell carcinoma (OSCC). A whole transcriptomic analysis was performed on a group of seven matched samples encompassing NOM, OSF, OSFSCC, and OSCC.
    Results: We observed significantly decreased expression of E-cadherin and PanCK, while N-cadherin, vimentin, α-SMA, and CD44 showed significantly higher expression in OSFSCC and OSCC as compared to OSF, both at protein and RNA levels. CD44 expression was noticeably higher in OSFSCC (p < 0.001) than in OSCC.
    Conclusion: Downregulation of epithelial markers with concomitant upregulation of mesenchymal and stem cell markers suggests the potential role of EMT and stemness in accelerating the pathogenesis and malignant transformation of OSF. The high levels of CD44 expression seen in OSFSCC indicate a high propensity for aggressiveness and acquisition of stem-like characteristics by the cells undergoing EMT.
    Language English
    Publishing date 2024-01-01
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2212-4268
    ISSN 2212-4268
    DOI 10.1016/j.jobcr.2023.12.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Understanding the molecular mechanism associated with reversal of oral submucous fibrosis targeting hydroxylysine aldehyde-derived collagen cross-links.

    Shetty, Smitha Sammith / Sharma, Mohit / Kabekkodu, Shama Prasada / Kumar, Nv Anil / Satyamoorthy, Kapaettu / Radhakrishnan, Raghu

    Journal of carcinogenesis

    2021  Volume 20, Page(s) 9

    Abstract: Fibrosis is a pathological state characterized by excessive deposition of the extracellular matrix components leading to impaired tissue function in the affected organ. It results in scarring of the affected tissue akin to an over-healing wound as a ... ...

    Abstract Fibrosis is a pathological state characterized by excessive deposition of the extracellular matrix components leading to impaired tissue function in the affected organ. It results in scarring of the affected tissue akin to an over-healing wound as a consequence of chronic inflammation and repair in response to injury. Persistent trauma of susceptible oral mucosa due to habitual chewing of betel quid resulting in zealous healing of the mucosal tissue is one plausible explanation for the onset of oral submucous fibrosis (OSF). The irreversibility and resistance of collagen to degradation and its high potential to undergo malignant change are a major reason for morbidity in OSF. Hence, early diagnosis and timely treatment are crucial to prevent the progression of OSF to malignancy. This review focuses on the mechanistic insight into the role of collagen cross-links in advancing fibrosis and possible therapeutic targets that bring about a reversal of fibrosis. These options may be beneficial if attempted as a specific therapeutic modality in OSF as is in organ fibrosis. The upregulation of lysyl oxidase and lysyl hydroxylase has been shown to exhibit the higher levels of the hydroxylysine aldehyde-derived cross-links in fibrosis and tumor stroma promoting the tumor cell survival, resistance, and invasion. The
    Language English
    Publishing date 2021-08-13
    Publishing country India
    Document type Journal Article ; Review
    ZDB-ID 2098237-9
    ISSN 1477-3163 ; 1477-3163 ; 0974-6773
    ISSN (online) 1477-3163
    ISSN 1477-3163 ; 0974-6773
    DOI 10.4103/jcar.JCar_24_20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Role of Yes-associated protein and transcriptional coactivator with PDZ-binding motif in the malignant transformation of oral submucous fibrosis.

    Sharma, Mohit / Hunter, Keith D / Fonseca, Felipe Paiva / Shetty, Smitha Sammith / Radhakrishnan, Raghu

    Archives of oral biology

    2021  Volume 128, Page(s) 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 ...

    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.
    MeSH term(s) Cell Movement ; Epithelial-Mesenchymal Transition ; Fibrosis ; Humans ; Oral Submucous Fibrosis ; Trans-Activators
    Chemical Substances Trans-Activators
    Language English
    Publishing date 2021-05-23
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 80227-x
    ISSN 1879-1506 ; 0003-9969
    ISSN (online) 1879-1506
    ISSN 0003-9969
    DOI 10.1016/j.archoralbio.2021.105164
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Biological implications of the immune factors in the tumour microenvironment of oral cancer.

    Shetty, Smitha Sammith / Padam, Kanaka Sai Ram / Hunter, Keith D / Kudva, Adarsh / Radhakrishnan, Raghu

    Archives of oral biology

    2021  Volume 133, Page(s) 105294

    Abstract: Objective: The objective of this review is to decipher the biological implications of the immune factors in the tumour microenvironment in oral cancer. The restoration of balance between tumour tolerance and tumour eradication by the host immune cells ... ...

    Abstract Objective: The objective of this review is to decipher the biological implications of the immune factors in the tumour microenvironment in oral cancer. The restoration of balance between tumour tolerance and tumour eradication by the host immune cells is critical to provide effective therapeutic strategies.
    Design: The specific role of the stromal and the immune components in oral cancer was reviewed with a tailored search strategy using relevant keywords. The articles were retrieved from bibliometric databases indexed in PubMed, Scopus, and Embase. An in silico analysis was performed to identify potential drug candidates for immunotherapy, by accessing the Drug-Gene Interactions Database (DGIdb) using the rDGIdb package.
    Results: There is compelling evidence for the role of the cellular and extracellular components of the tumour microenvironment in inducing immunosuppression and progression of oral cancer. The druggable candidates specifically targeting the immune system are a viable option in the treatment of oral cancer as they can regulate the tumour microenvironment.
    Conclusion: A complex interaction between the tumour and the immunological microenvironment influences the disease outcome in oral cancer. Targeting specific components of the immune system might be relevant, as immunotherapy may become the new standard of care for oral cancer.
    MeSH term(s) Humans ; Immunologic Factors ; Immunotherapy ; Mouth Neoplasms/therapy ; Tumor Microenvironment
    Chemical Substances Immunologic Factors
    Language English
    Publishing date 2021-10-24
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 80227-x
    ISSN 1879-1506 ; 0003-9969
    ISSN (online) 1879-1506
    ISSN 0003-9969
    DOI 10.1016/j.archoralbio.2021.105294
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ul III Zs.151: Show issues Location:
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  5. Article: Signaling pathways promoting epithelial mesenchymal transition in oral submucous fibrosis and oral squamous cell carcinoma.

    Shetty, Smitha Sammith / Sharma, Mohit / Fonseca, Felipe Paiva / Jayaram, Pradyumna / Tanwar, Ankit Singh / Kabekkodu, Shama Prasada / Kapaettu, Satyamoorthy / Radhakrishnan, Raghu

    The Japanese dental science review

    2020  Volume 56, Issue 1, Page(s) 97–108

    Abstract: 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 ... ...

    Abstract 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.
    Language English
    Publishing date 2020-08-22
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2439945-0
    ISSN 1882-7616
    ISSN 1882-7616
    DOI 10.1016/j.jdsr.2020.07.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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