Methylation status of insulin-like growth factor-binding protein 7 concurs with the malignance of oral tongue cancer

Background: aberrant insulin-like growth factor-binding protein 7 (igfbp-7) expression has been found in various cancers such as prostate,breast,and colon. igfbp-7 induced the apoptosis of tumor and potentially predicted the clinical outcome in some cancers is further demonstrated. this study investigates the causes and underlying mechanisms of aberrant igfbp-7 expression in unravelling head and neck squamous cell carcinoma (hnscc). methods: a total of 47 oral tongue cancer patient samples were primarily analyzed for the methylation status in 5′ region of igfbp-7 by methylation-specific pcr (ms-pcr). subsequently the invasion,overexpression,and knockdown of igfbp-7 in the hnscc a253 invasive subpopulation were employed to examine the effect of igfbp-7. the epithelial-mesenchymal transition (emt) marker genes and akt/gsk3β/β-catenin signaling were further evaluated by western blot for the understanding the role of aberrant igfbp-7 expression and thereof putative mechanism. results: emt expressed in the invasive subpopulation of hnscc cell lines (a253 and rpmi 2650) was contemporary with the down-regulation of igfbp-7. after treatment with 5-aza-2′ deoxycytidine,the de-methylated cpg sites in the 5′ region of igfbp-7 were observed and igfbp-7 mrna expression was also restored. accordingly,re-expression igfbp-7 in invasive subpopulation of a253 could induce the mesenchymal-epithelial transition (met) and concurrently inhibited the cell invasion. moreover,igfbp-7 methylation status of 47 oral tongue tumors showed a positive correlation to invasive depth of the tumor,loco-regional recurrence,and cancer sequence. conclusions: igfbp-7 can alter emt relative marker genes and suppress cell invasion in a253 cell through akt/ gsk3β/β-catenin signaling. the epigenetic control of igfbp-7 in the invasion and metastasis of hnscc was reported,suggesting that igfbp-7 could be a prognostic factor for the probability of invasion and a therapeutic remedy. © 2015 chen et al.