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; Satyamoorthy, Kapaettu; Radhakrishnan, Raghu

doi:10.1016/j.jdsr.2020.07.002

Cited by 30 publications

(31 citation statements)

References 159 publications

(176 reference statements)

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“…Likewise, chrysophanol also inhibited SAS cell invasion ability (Figure 3), but it was reversed by IL-6 and IL-8 treatment (Figure 3A,B), further confirming that the effects were IL-6-and IL-8-dependent. Previous studies have reported that regulation of oral cancer metastasis involves many signaling pathways, such as MAPK, PI3K/AKT, and FAK/Src [51,52]. Recently, IL-6 has been shown to stimulate migration of oral cancer cells via the phosphorylation of STAT3 [45].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 and Interleukin-8 Regulate STAT3 Activation Migration/Invasion and EMT in Chrysophanol-Treated Oral Cancer Cell Lines

Hsu

Chen²,

Cheng³

et al. 2021

Life

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The tumor microenvironment plays a critical role in the control of metastasis. The epithelial–mesenchymal transition (EMT) is strongly associated with tumor metastasis, and consists of several protein markers, including E-cadherin and vimentin. We discovered that chrysophanol causes oral cancer cell apoptosis and the inhibition of migration/invasion and EMT. However, the detailed mechanisms of chrysophanol and its role in oral cancer with respect to the tumor microenvironment remain unknown. In the clinic, proinflammatory cytokines, such as IL-6 and IL-8, exhibit a higher expression in patients with oral cancer. However, the effect of chrysophanol on the production of IL-6 and IL-8 is unknown. We evaluated the expression of IL-6 and IL-8 in human SAS and FaDu oral cancer cell lines in the presence or absence of chrysophanol. The migration and invasion abilities were also determined using a Boyden chamber assay. Our results showed that treatment with chrysophanol significantly decreased the expression of IL-6 and IL-8, as well as the invasion ability of oral cancer cells. Moreover, chrysophanol also attenuated the EMT by increasing the expression of E-cadherin and reducing the expression of vimentin. Mechanistically, chrysophanol inhibited IL-6- and IL-8-induced invasion and STAT3 phosphorylation. IL-6 and IL-8 promote EMT and cell invasion, which is potentially related to the STAT3 signaling pathway in oral cancer. These findings provide insight into new aspects of chrysophanol activity and may contribute to the development of new therapeutic strategies for oral cancer.

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Section: Discussionmentioning

confidence: 99%

Interleukin-6 and Interleukin-8 Regulate STAT3 Activation Migration/Invasion and EMT in Chrysophanol-Treated Oral Cancer Cell Lines

Hsu

Chen²,

Cheng³

et al. 2021

Life

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“… 36 EMT markers, which are mediators of EMT regulated complex signalling pathways have detrimental role in the pathogenesis of OSF and OSCC. 37 IGF‐I/IGF‐IR signalling is associated EMT progression in various type of cancers. 38 Our data indicated that OSF remarkably increased the cell‐matrix adhesion, invasion and migration abilities and the activity of MMP‐2 of oral cancer and affected the EMT by enhancing the expression of N‐cadherin, fibronectin and vimentin and downregulating the expression of E‐cadherin in human oral cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Oral submucous fibrosis stimulates invasion and epithelial‐mesenchymal transition in oral squamous cell carcinoma by activating MMP‐2 and IGF‐IR

Chen

Lin

Chang

2021

J Cellular Molecular Medi

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Cancer growth is determined by cell proliferation and relies on the microenvironment of the tumour, which has been recently considered as an attractive target for new anti-tumour therapies. 1 The microenvironment of oral squamous cell carcinoma (OSCC) contains many different cell populations, including immune cells, endothelial cells, fibroblasts and non-cell components of the extracellular matrix. 2,3 Fibroblasts are the most abundant stromal cells in the tumour microenvironment and can secret a wide spectrum of cytokines and chemokines into the invasive margins of desmoplastic cancers to promote cancer development and activate metastasis. 4 Recently, collagen cross-linking and the expression of key enzymes, including lysyl hydroxylase 2 or lysyl oxidase (LOX) and LOX-like 2 were

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“…As disease progressed, the fibers increased in thickness and involved the deeper submucosal region[ 35 ] and collagen III and IV are replaced with Type I. [ 36 ]…”

Section: Discussionmentioning

confidence: 99%

New Insights for Consummate Diagnosis and Management of Oral Submucous Fibrosis Using Reactive and Reparative Fibrotic Parameter Derived Algorithm

Ramadoss

Rajkumar

Vasanthi

et al. 2021

Journal of Pharmacy and Bioallied Sciences

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Objective: Reproducibility of qualitative changes in histopathological diagnosis involving narrow variation is often challenging. This study aims to characterize the histological fibrotic events in detail so as to derive an in-depth multiparametric algorithm with individually quantified histological parameters for effective monitoring of the. disease process in oral submucous fibrosis and for potential therapeutic targets for early intervention. Methods: Formalin fixed paraffin embedded (FFPE) blocks of oral submucous fibrosis (OSMF), were taken and sections were stained with Hematoxylin & Eosin stain and Masson Trichrome stain. Photomicrographs were assessed for various morphometric parameters with Image J software version 1.8. Linear Regression was used to model the relationship using Inflammatory Cell Count, Extent of Inflammation collagen stained area, Epithelial thickness integrated density of collagen, MVPA, Area, Perimeter, were taken as variables. Result: Inflammatory cell count and the extent of inflammation also decreased with increasing grades of OSMF. Collagen proportionate area, integrated collagen density and epithelial thickness were compared among different grades of OSMF. Grade IV OSMF had greatest mean collagen proportionate area , highest integrated collagen density and lowest epithelial thickness when compared to other grades of OSMF. Linear regression model revealed smaller variation between Grade I to Grade II. Whereas Grade II to Grade IV exhibited larger variation suggestive of increased growth rate and all the coefficients were found to lie within 95% confidence limits Conclusion: Diagnostic algorithm with multiparametric regression model were derived and combinatorial therapeutic approaches have been suggested for more effective management of oral submucous fibrosis

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

Cited by 30 publications

References 159 publications

Interleukin-6 and Interleukin-8 Regulate STAT3 Activation Migration/Invasion and EMT in Chrysophanol-Treated Oral Cancer Cell Lines

Interleukin-6 and Interleukin-8 Regulate STAT3 Activation Migration/Invasion and EMT in Chrysophanol-Treated Oral Cancer Cell Lines

Oral submucous fibrosis stimulates invasion and epithelial‐mesenchymal transition in oral squamous cell carcinoma by activating MMP‐2 and IGF‐IR

New Insights for Consummate Diagnosis and Management of Oral Submucous Fibrosis Using Reactive and Reparative Fibrotic Parameter Derived Algorithm

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