BackgroundThe 5-year overall survival rates for head and neck cancer (HNC) relies on distant metastasis. Importantly, the epithelial-mesenchymal transition (EMT) is believed to be an initial step of metastasis. However, the relationship of epigenetic with EMT formation is still unexplored in HNC. This study focuses on invasive subclones of HNC cell lines through the simulation of invasion in vitro; and underlying mechanisms were analyzed including DNA methylation and gene expression profile.MethodsInvasive subclones of NHC cell lines were successfully obtained using transwell coated with Matrixgel. Cells invaded through 8 μm pore several times were subcultured and examined with EMT features including morphology, EMT marker genes expression, and invasive ability. Moreover, compared the profile of genes expression in parental and invasive cells was analyzed using mRNA expression array.ResultsDNA methyltransferase 3B (DNMT 3B) was upregulated in invasive subclones and might control the 5′ region of E-cadherin (E-cad) methylation and further inhibited E-cad protein expression. Interference of DNMT 3B by siRNA or miRNA 29b could reduce EMT and cell invasion. Expression array analysis revealed the most possible involved pathways in cell invasion including arginine and proline metabolism, TGF-beta, and focal adhesion.ConclusionsDNMT 3B might control EMT by DNA methylation manner in invasive HNC cell lines. Moreover, miR-29b mimic downregulated DNMT 3B and inhibited EMT and cell invasion indicated the role of therapeutic agent for invasive HNC. Genes identified from array data and new molecules are involved in metastasis of HNC need further validation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2468-x) contains supplementary material, which is available to authorized users.

The antimigratory effects of resveratrol by reduced MMP expression through the inhibition of Rac1, p-FAK, and lamellipodia formation and the activation of p-AKT and p-ERK1/2 suggest that resveratrol is a potential compound for the treatment of vascular diseases via the regulation of VSMC migration.

BackgroundAberrant 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).MethodsA 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.ResultsEMT 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.ConclusionsIGFBP-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0138-5) contains supplementary material, which is available to authorized users.