BackgroundThe epithelial-to-mesenchymal transition (EMT) process results in a loss of cell-cell adhesion, increased cell mobility, and is crucial for enabling the metastasis of cancer cells. Recently, the enzyme SIRT1 has been implicated in a variety of physiological processes; however, its role in regulating oral cancer metastasis and EMT is not fully elucidated. Here, we propose a mechanism by which the enzyme sirtuin1 (SIRT1) regulates the EMT process in oral cancer by deacetylating Smad4 and repressing the effect of TGF-β signaling on matrix metalloproteinase-7 (MMP7).MethodsThe roles of SIRT1 in tumor cell migration/invasion and metastasis to the lungs were investigated using the Boyden chamber assay and orthotopic injections, respectively. RNA interference was used to knockdown either SIRT1 or Smad4 expression in oral squamous cell carcinoma (OSCC) cell lines. Immunoblotting, zymographic assays, and co-immunoprecipitation were used to examine the effects of SIRT1 overexpression on MMP7 expression and activity, as well as on SIRT1/ Smad4 interaction.ResultsWe found that compared with normal human oral keratinocytes (HOKs), SIRT1 was underexpressed in OSCC cells, and also in oral cancer tissues obtained from 14 of 21 OSCC patients compared with expression in their matched normal tissues. Overexpression of SIRT1 inhibited migration of OSCC cells in vitro, as well as their metastasis to the lung in vivo. Furthermore, up-regulation of SIRT1 in metastatic OSCCs significantly inhibited the migration and invasion abilities of OSCC cells, while concomitantly increasing the expression of E-cadherin, and decreasing the expressions of mesenchymal markers. We also identified Smad4, a TGF-β-activated transcription factor, as a direct target protein for SIRT1. Overexpression of SIRT1 in OSCC cells led to decreased levels of acetylated Smad4, and inhibition of TGF-β-induced signaling. By associating and deacetylating Smad4, SIRT1 enzyme can influence MMP7 expression, MMP enzyme activity, and consequently, cell migration, invasion, and tumor metastasis in OSCCs.ConclusionsThese findings provide a valuable insight into the potential role of the SIRT1 enzyme in regulating cell migration and invasion in oral squamous cell carcinoma. Our findings suggest the SIRT1/Smad4/MMP7 pathway as a target for oral cancer driven by EMT.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-254) contains supplementary material, which is available to authorized users.

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The aim of this study was to identify the health hazards and possible exposure surveillance markers of workers exposed to nanoparticles during manufacturing and application in comparison to a group of unexposed workers. For this longitudinal study, we recruited 158 nanomaterial-handling workers and 104 non-exposed workers from 14 manufacturing plants in Taiwan (baseline). Among them, 124 nanomaterial-handling workers and 77 unexposed workers were monitored 6 months later. We investigated pulmonary and cardiovascular disease markers, inflammation and oxidative stress markers, antioxidant enzymes and genotoxicity markers. Antioxidant enzymes (superoxide dismutase, glutathione peroxidase) and cardiovascular markers (vascular cell adhesion molecule, paraoxonase) were significantly associated with nanomaterial-handling during the 6-month follow-up period. In addition, the small airway damage marker (Clara cell protein 16) and lung function test parameters were also significantly associated with handling nanomaterials. The study markers and lung function tests are possible markers that could be useful for surveillance of nanomaterial-handling workers.

Non-synonymous SNP rs3733591 variant within the SLC2A9 gene from two geographically diverse populations served as an important genetic checkpoint for tophaceous gout and increased uric acid levels.