Growth‐regulated oncogene‐α from oral submucous fibrosis fibroblasts promotes malignant transformation of oral precancerous cells

Ye, Mei Yin; Chen, Meng Yen; Chang, Ya Han; Huang, Jow-Lay; Huang, Tze Ta; Wong, Tung Yiu; Hong, Tse-Ming; Chen, Yuh Ling

doi:10.1111/jop.12768

Cited by 9 publications

(10 citation statements)

References 30 publications

(54 reference statements)

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“…It was found that oral sub-mucous fibrosis related fibroblasts expressed higher level of CXCL1 than normal fibroblasts and CXCL1 might function as a pre-cancerous promoter. 26 On the contrary, in patients diagnosed of gastric cancer with precancerous lesions, level of serum CXCL1 was significantly reduced while other inflammatory cytokines like IL-1, IL-6 were increased compared with control group, indicating the systematic activation of the immune system and an unusual activation pathway of CXCL1. 27 Though here we found precancerous lesions on tongue had statistical significance in prediction of lymphatic metastasis and OS, its clinical significance whether it could be a predictor in prognosis of OTSCC should need further exploration.…”

Section: Discussionmentioning

confidence: 86%

“…Additionally, patients already diagnosed with OTSCC yet accompanied by another precancerous lesion on tongue were found to be related with higher risk of lymphatic metastasis and poorer prognosis than those who had no precancerous lesion on tongue. It was found that oral sub‐mucous fibrosis related fibroblasts expressed higher level of CXCL1 than normal fibroblasts and CXCL1 might function as a pre‐cancerous promoter 26 . On the contrary, in patients diagnosed of gastric cancer with precancerous lesions, level of serum CXCL1 was significantly reduced while other inflammatory cytokines like IL‐1, IL‐6 were increased compared with control group, indicating the systematic activation of the immune system and an unusual activation pathway of CXCL1 27 .…”

Section: Discussionmentioning

confidence: 97%

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CXCL1 promoted the migration and invasion abilities of oral cancer cells and might serve as a promising marker of prognosis in tongue cancer

Zhang

Dong

Zhao

et al. 2023

J Oral Pathology Medicine

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BackgroundOral tongue squamous cell carcinoma tends to metastasize to cervical lymphatic nodes early which leads to a 50% drop of survival rate. CXCL1 could be secreted by LNMTca8113 cell induced lymphatic endothelial cells and promoted LNMTca8113 cell migration. The current study aimed to further explore the effect of CXCL1 on the proliferation and migration abilities of tongue cancer cells and the prognostic value of serum CXCL1 in oral tongue squamous cell carcinoma.MethodsCell proliferation and migration ability were analysed by CCK8 assays and transwell migration assays. Immunofluorescence technique was used to show cytoskeleton. GST pull‐down assay was applied to quantify the activation of GTPases. Blood samples of patients were collected and clinicopathological characteristics were analysed.ResultsCXCL1 could promote cancer cell proliferation in appropriate concentration by PI3K/AKT pathway. It also regulated the activation of Rho GTPases to mediate the rearrangements of cytoskeleton to promote tumour cell migration. Level of plasma CXCL1 could predict the possibility of early lymphatic metastasis and had a predictive value in progression‐free survival and overall survival.ConclusionsCXCL1 could promote oral cancer cell proliferation, migration and invasion in vitro and contributed theoretical knowledge for the target selection in molecular targeted therapy. Level of plasma CXCL1 might serve as a biomarker for prognosis in oral tongue squamous cell carcinoma patients.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 97%

CXCL1 promoted the migration and invasion abilities of oral cancer cells and might serve as a promising marker of prognosis in tongue cancer

Zhang

Dong

Zhao

et al. 2023

J Oral Pathology Medicine

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“…36 ROS may lead to doublestrand DNA breaks (DS-breaks) of epithelial cells leading to their malignant transformation. 36 The GRO-α secretion by OSF myofibroblasts via EGFR/ERK signaling, F-actin rearrangement, and stemness, 37 malignant transformation of the dysplastic oral keratinocytes through its CXCR-2 receptor. A recent paper published by Kim et al 38 has shown that CXCL-1, secreted by oral cancer cells in a paracrine manner promotes senescence in fibroblasts, and further propagates its senescent state via secretion of CXCL-1, and thereby establishes an autocrine loop (Figure 2, orange box).…”

Section: Molecular Orchestrators Of Senescence Associated Secretory Phenotypementioning

confidence: 99%

Emerging role of cellular senescence in the pathogenesis of oral submucous fibrosis and its malignant transformation

Sharma¹,

Hunter

Fonseca

et al. 2021

Head & Neck

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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.

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“…116 These MSCs can serve as a source of multipotent cells that can rapidly repopulate the wound in response to epithelial injury. 116 Ye et al 117 showed that growth-regulated oncogene-α (GRO-α) secretion by OSF fibroblasts promotes oral keratinocyte malignant transformation by augmenting EGFR/ERK signalling, F-actin rearrangement and stemness. Transformed keratinocytes can then acquire further genetic alterations with the evolution of more invasive clones.…”

Section: Rise Of Cancer Stem Cells-dichotomy Of Areca Nut Ingredientsmentioning

confidence: 99%

Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation

Sharma¹,

Fonseca

Hunter

et al. 2020

Int J Oral Sci

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The integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.

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Growth‐regulated oncogene‐α from oral submucous fibrosis fibroblasts promotes malignant transformation of oral precancerous cells

Abstract: GRO-α from OSF-associated fibroblasts paracrinally promotes oral malignant transformation and significantly contributes to OSCC development.

Cited by 9 publications

References 30 publications

CXCL1 promoted the migration and invasion abilities of oral cancer cells and might serve as a promising marker of prognosis in tongue cancer

CXCL1 promoted the migration and invasion abilities of oral cancer cells and might serve as a promising marker of prognosis in tongue cancer

Emerging role of cellular senescence in the pathogenesis of oral submucous fibrosis and its malignant transformation

Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation

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