<i>Retracted:</i> Arecoline induces epithelial‐mesenchymal transformation and promotes metastasis of oral cancer by SAA1 expression

Ren, Hui; He, Guoqin; Lu, Zhiyuan; He, Qiuming; Li, Shuai; Huang, Zhexun; Chen, Zheng; Cao, Congyuan; Wang, Anxun

doi:10.1111/cas.14866

Cited by 26 publications

(31 citation statements)

References 41 publications

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“…A great deal of studies have shown that the development of OSF has been intimated to chewing betel nut commodity [ 31 ]. Arecoline is the major areca nut alkaloid and has been classified as carcinogenic to humans; it is also considered the main causative factor of OSF due to chewing betel nut [ 32 , 33 ]. However, how arecoline promotes OSF progression is unclear.…”

Section: Discussionmentioning

confidence: 99%

Identification of a BRAF/PA28γ/MEK1 signaling axis and its role in epithelial-mesenchymal transition in oral submucous fibrosis

Xie

Hua

et al. 2022

Cell Death Dis

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Oral submucous fibrosis (OSF) is a chronic and insidious oral potentially malignant disorder associated with a 4–17% risk of oral squamous cell carcinoma (OSCC). Our previous study found that proteasomal activator 28 gamma (PA28γ) is frequently overexpressed in oral squamous cell carcinoma and negatively correlated with poor patient prognosis. However, the role of PA28γ in the occurrence and development of OSF remains unclear. Here, we screened PA28γ-related genes and investigated their function in OSF. We demonstrated that the expression of PA28γ was positively associated with MEK1 and gradually elevated from normal to progressive stages of OSF tissue. Arecoline, a pathogenic component of OSF, could upregulate the protein levels of PA28γ and phosphorylated MEK1 and contribute to epithelial to mesenchymal transition (EMT) in epithelial cells. Notably, PA28γ could interact with MEK1 and upregulate its phosphorylation level. Furthermore, arecoline upregulated BRAF, which can interact with PA28γ and upregulate its protein level. Additionally, BRAF, PA28γ, and MEK1 could form protein complexes and then enhance the MEK1/ERK signaling pathways. The concrete mechanism of the protein stability of PA28γ is that BRAF mediates its degradation by inhibiting its ubiquitination. These findings underscore the instrumental role of PA28γ in the BRAF/MEK1 pathway and enhanced EMT through MEK1/ERK activation in OSF.

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Section: Discussionmentioning

confidence: 99%

Identification of a BRAF/PA28γ/MEK1 signaling axis and its role in epithelial-mesenchymal transition in oral submucous fibrosis

Xie

Hua

et al. 2022

Cell Death Dis

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“…Saa1 and Saa2 genes encode serum amyloid A proteins Saa1 and Saa2, both of which are acute phase proteins [70] . Saa1 and Saa2 have been associated with pancreatic, renal, lung, colorectal, ovarian, oral, gastric, and breast cancer as well glioblastoma [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] . Although the increase in Saa1 and Saa2 proteins are typically attributed to tumor-associated inflammation, studies have shown that Saa1 can regulate Akt signaling in tumor cells and siRNA knockdown of Saa1 in pancreatic cells inhibits migration/invasion and epithelial to mesenchymal transition [ 71 , 79 ].…”

Section: Discussionmentioning

confidence: 99%

Transgenic overexpression of the miR-200b/200a/429 cluster inhibits mammary tumor initiation

Watson

Moorehead

2021

Translational Oncology

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“…Enhanced glycolysis and weakened tricarboxylic acid (TCA) cycle are the key factors in regulating CAF proliferation ( 18 , 19 ). Researchers found that arecoline could promote glycolysis leading to the increase of reactive oxygen species, which could inhibit the TCA cycle and mediate tumor metastasis ( 20 , 21 ). Arecoline also led to a disordered progression of cellular aerobic metabolism by destroying cytoskeletal integrity and mitochondrial function ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

Arecoline Is Associated With Inhibition of Cuproptosis and Proliferation of Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma: A Potential Mechanism for Tumor Metastasis

Chen

Liao

et al. 2022

Front. Oncol.

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BackgroundMetastatic disease remains the primary cause of death in patients with oral squamous cell carcinoma (OSCC), especially those who use betel nut. The different steps of the metastatic cascade rely on reciprocal interactions between cancer cells and the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are regarded as a significant component in the TME of OSCC. However, the precise mechanisms regulating CAFs in OSCC are poorly understood.MethodsThirteen genes related to the arecoline were analyzed to explore the significant ones involved in arecoline-related OSCC metastasis. The GSE139869 (n = 10) and The Cancer Genome Atlas (TCGA)-OSCC data (n = 361) were mined for the identification of the differentially expressed genes. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the independent prognostic signatures. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the functional enrichment of selected genes, and gene set enrichment analysis of cuproptosis-related genes was completed. Spearman’s analysis and Tumor Immune Estimation Resource (TIMER) were used to visualize the correlation between the infiltration of CAFs and the gene expression. The correlation analysis of the cells and different genes, including CAF infiltration and transcripts per million expression, was assessed. The relationship between arecoline and CAFs was confirmed by cell counting kit-8 assay (CCK-8). CancerSEA was searched to identify the single-cell phenotype.ResultArecoline-associated fibrosis-related OSCC differentially expressed genes (AFOC-DEGs), namely, PLAU, IL1A, SPP1, CCL11, TERT, and COL1A2, were screened out and selected from the Gene Expression Omnibus (GEO) database and TCGA database. AFOC-DEGs were highly expressed in OSCC, which led to poor survival of patients. Functional enrichment analysis, protein–protein interaction network construction, and Spearman’s correlation analysis all suggested that AFOC-DEGs were closely associated with cuproptosis. Cellular experiments demonstrated that arecoline stimulation could significantly increase the cell viability of CAFs. Single-sample Gene Set Enrichment Analysis (ssGSEA) results showed that GLS and MTF1 were highly expressed when fibroblasts proliferated at high enrichment levels. In addition, analysis of single-cell sequencing results suggested that OSCC cells with high expression of AFOC-DEGs were associated with OSCC metastasis.ConclusionWe found a close association between arecoline, cuproptosis, and CAFs, which might play an important role in the metastasis of OSCC.

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Retracted: Arecoline induces epithelial‐mesenchymal transformation and promotes metastasis of oral cancer by SAA1 expression

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 26 publications

References 41 publications

Identification of a BRAF/PA28γ/MEK1 signaling axis and its role in epithelial-mesenchymal transition in oral submucous fibrosis

Identification of a BRAF/PA28γ/MEK1 signaling axis and its role in epithelial-mesenchymal transition in oral submucous fibrosis

Transgenic overexpression of the miR-200b/200a/429 cluster inhibits mammary tumor initiation

Arecoline Is Associated With Inhibition of Cuproptosis and Proliferation of Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma: A Potential Mechanism for Tumor Metastasis

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