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Limited studies have been conducted on the role of OSF in relation to the invasive capabilities and epithelial\u2010mesenchymal transition (EMT) in oral cancer. Herein, we investigated the effects of OSF on the microenvironment of human oral cancer cells. The results showed that the conditioned medium (CM) of fibrotic buccal mucosal fibroblasts (fBMFs) strongly induced the invasion of oral cancer cells and increased the activities of matrix metalloproteinase\u20102. OSF significantly induced the EMT in oral cancer cells and downregulated epithelial markers, such as E\u2010cadherin, but significantly elevated vimentin, fibronectin, N\u2010cadherin, RhoA, Rac\u20101 and FAK. Insulin\u2010like growth factor\u20101 (IGF\u20101) was elevated in OSF. The protein levels of the IGF\u20101R were upregulated specifically in fBMF CM treatment for oral cancer cells, and the IGFR gene was confirmed by The Cancer Genome Atlas patient transcriptome data. The Kaplan\u2010Meier curve analysis revealed that patients with oral squamous cell carcinoma and high IGFR expression levels had poorer 5\u2010year survival than those with low IGFR expression (<jats:italic>p<\/jats:italic> = 0.004). The fBMF\u2010stimulated EMT cell model may recapture some of the molecular changes during EMT progression in clinical patients with oral cancer.<\/jats:p>","DOI":"10.1111\/jcmm.16929","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T05:40:30Z","timestamp":1631770830000},"page":"9814-9825","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Oral submucous fibrosis stimulates invasion and epithelial\u2010mesenchymal transition in oral squamous cell carcinoma by activating MMP\u20102 and IGF\u2010IR"],"prefix":"10.1111","volume":"25","author":[{"given":"Pei\u2010Ni","family":"Chen","sequence":"first","affiliation":[{"name":"Clinical Laboratory Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"Institute of Medicine Chung Shan Medical University Taichung 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