Local invasiveness and distant metastasis are critical factors that contribute to oral squamous cell carcinoma-related deaths. Increasing evidence has shown that the epithelial to mesenchymal transition (EMT) is involved in cancer progression and is associated with the 'stemness' of cancer cells. Snail is a transcriptional factor that can induce EMT and preserve stem-cell function, which may induce resistance to radio-and chemotherapies in the cells. In the present study, SCC9 cells were transfected with an empty vector or a vector encoding human Snail (SCC9-S). Overexpression of Snail induced SCC9 cells to undergo EMT, in which the cells presented a fibroblast-like appearance, downregulated the epithelial markers E-cadherin and b-catenin, upregulated the mesenchymal marker vimentin, and associated with highly invasive and metastatic properties. Furthermore, the induction of EMT promoted cancer stem cell (CSC)-like characteristics in the SCC9-S cells, such as low proliferation, self-renewal, and CSC-like markers expression. These results indicate that overexpression of Snail induces EMT and promotes CSC-like traits in the SCC9 cells. Further understanding the role of Snail in cancer progression may reveal new targets for the prevention or therapy of oral cancers. Oral squamous cell carcinoma (OSCC) is the most frequent type of cancer in the oral cavity and is associated with high morbidity and poor prognosis. 1,2 Despite progress in surgery, chemotherapy, and radiotherapy, the 5-year survival rate has remained at 50-55% over the past several decades. 3 Local or regional recurrences and distant metastases have a critical role in this process, and the mechanism underlying their occurrence remains poorly understood. 2,4 During metastatic progression, tumour cells lose cell-cell adhesion, detach from the primary site, invade the basement membrane, survive and circulate in the blood vessels, leave the bloodstream, and finally colonise in a new host environment to form micrometastases. 2,5-7 A growing body of research strongly suggests that the epithelial to mesenchymal transition (EMT), which occurs normally during embryonic development, tissue remodelling, and wound healing, is a critical early event in tumour invasion and metastasis. [8][9][10] It is characterised by downregulation of epithelial markers, such as E-cadherin, and upregulation of mesenchymal markers, such as vimentin. During the process of EMT, epithelial cells acquire mesenchymal cell properties and show reduced intercellular adhesion and increased invasion. 11 The transcriptional repressor Snail, which is a zinc finger protein, first described in Drosophila melanogaster, can bind to the E-boxes in the human E-cadherin promoter and suppress its transcription. 12,13 Snail has previously been implicated in triggering EMT during embryonic development, fibrosis, and tumour progression. 14 This process also occurs in the progression of carcinomas (including oral carcinoma cells), following the downregulation of E-cadherin expression or co-expression of NB...

BackgroundThe epithelial-to-mesenchymal transition (EMT) is a key process in carcinogenesis, invasion, and metastasis of oral squamous cell carcinoma (OSCC). In our previous studies, we found that neuropilin-1 (NRP1) is overexpressed in tongue squamous cell carcinoma and that this overexpression is associated with cell migration and invasion. Nuclear factor-kappa B (NF-κB) plays an essential role both in the induction and the maintenance of EMT and tumor metastasis. Therefore, we hypothesized that NRP1 induces EMT, and that NRP1-induced migration and invasion may be an important mechanism for promoting invasion and metastasis of OSCC through NF-κB activation.Methods/ResultsThe variations in gene and protein expression and the changes in the biological behavior of OSCC cell lines transfected with a vector encoding NRP1, or the corresponding vector control, were evaluated. NRP1 overexpression promoted EMT and was associated with enhanced invasive and metastatic properties. Furthermore, the induction of EMT promoted the acquisition of some cancer stem cell (CSC)-like characteristics in OSCC cells. We addressed whether selective inhibition of NF-κB suppresses the NRP1-mediated EMT by treating cells with pyrrolidinedithiocarbamate ammonium (PDTC), an inhibitor of NF-κB. Immunohistochemical analysis of NRP1 in OSCC tissue samples further supported a key mediator role for NRP1 in tumor progression, lymph node metastasis, and indicated that NRP1 is a predictor for poor prognosis in OSCC patients.ConclusionOur results indicate that NRP1 may regulate the EMT process in OSCC cell lines through NF-κB activation, and that higher NRP1 expression levels are associated with lymph node metastasis and poor prognosis in OSCC patients. Further investigation of the role of NRP1 in tumorigenesis may help identify novel targets for the prevention and therapy of oral cancers.

A copper-catalyzed regiodivergent hydrosilylation of a wide range of simple allenes is reported. Linear and branched allylsilanes were formed by judicious choice of solvents. Furthermore, branched allylsilanes were obtained with high enantioselectivity (up to 97% enantiomeric excess) with the aid of a C2-symmetric bisphosphine ligand in the unprecedented asymmetric allene hydrosilylation.

IntroductionTo investigate the association of the interleukin-1β (IL-1β) (3953/4) C→T polymorphism with chronic periodontitis (CP) in Asians.Material and methodsSystematic searches of electronic databases and hand searching of references were performed, including PubMed, Embase, the Cochrane Library, and the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. Publication bias was tested by Egger's test. Sensitivity analysis was conducted by limiting the meta-analysis studies conforming to Hardy-Weinberg equilibrium (HWE). Data analyses were carried out using RevMan 6.0.ResultsA meta-analysis was performed on 20 published case-control studies, including 1,656 CP cases and 1,498 healthy controls. The pooled OR was 1.60 (95% CI = 1.02–2.52, p = 0.04) for the T allele carriers (TT + CT) compared with CC and 1.60 (95% CI = 1.06–2.42, p = 0.02) for T vs. C. Subgroup analysis by country revealed significant risks of CP among Indians carrying the T allele (TT vs. CC: OR = 3.88, 95% CI = 1.77–8.50, p = 0.0007).ConclusionsThe analysis showed that IL-1β (3953/4) C→T polymorphism probably increases the risk of CP in Asians, and the IL-1β+3954 TT genotype may be associated with a strongly increased risk of CP in Indians, but not in Chinese.

Semaphorin3A (SEMA3A), an axon guidance molecule in the nervous system, plays an inhibitory role in oncogenesis. Here, we investigated the expression pattern and biological roles of SEMA3A in head and neck squamous cell carcinoma (HNSCC) by gain-of-function assays using adenovirus transfection and recombinant human SEMA3A protein. In addition, we explored the therapeutic efficacy of SEMA3A against HNSCC in vivo. We found that lower expression of SEMA3A correlated with shorter overall survival and had independent prognostic importance in patients with HNSCC. Both genetic and recombinant SEMA3A protein inhibited cell proliferation and colony formation and induced apoptosis, accompanied by decreased cyclin E, cyclin D, CDK2, CDK4 and CDK6 and increased P21, P27, activated caspase-5 and caspase-7. Moreover, over-expression of SEMA3A suppressed migration, invasion and epithelial-to-mesenchymal transition due in part to the inhibition of NF-κB and SNAI2 in HNSCC cell lines. Furthermore, intratumoral SEMA3A delivery significantly stagnated tumor growth in a xenograft model. Taken together, our results indicate that SEMA3A serves as a tumor suppressor during HNSCC tumorigenesis and a new target for the treatment of HNSCC.