Interestingly, there are 2 E-box sequences in RELN promoter region, and we identified the recruitment of transcriptional repressor Snail to the RELN promoter after TGF-b1 treatment. In addition, we observed elevated expression of RELN mRNA after treatment with the histone deacetylase inhibitor, TSA, in ESCC cells, and Snail was also reported to be interacted with HDAC1 to repress E-cadherin expression. And RELN promoter was epigenetically regulated through DNA methylation. Equally important in this context is the interplay between methylation, chromatin structure and histone deacetylation. Thus, we speculated that Snail might interact with various classes of histone deacetylases in complexes that repress RELN transcription and perhaps induce histone deacetylation in ESCC cells. Recently, several groups reported that loss of functional Reelin was implicated in motility and invasion of pancreatic, gastric, and breast cancer. Our previous study showed that Reelin was dysregulated in ESCC samples. In this study, knockdown of Reelin expression considerably enhanced mobility of ESCC cells, which is consistent with previous reports. Unfortunately, further examination on ESCC specimens failed to find a significant correlation between RELN expression and clinical metastasis status. One possible explanation is Oxysophocarpine that there are limited amount of metastatic cancer cells in the tested specimens. Another reason rests on multiple steps of metastasis. Because metastasis consists of a serial of procedures and we have not determined in which steps RELN may be involved. Therefore, the result in ESCC tissues is not necessarily in conflict with the finding that RELN suppressed cell migration of human ESCC cells. In summary, Reelin is involved in TGF-b1-mediated cell migration in ESCC cells, and the TGF-b1-induced migration could be suppressed by Reelin expression. We further demonstrated that Snail can regulate Reelin expression through binding to Reelin promoter region in vivo after TGF-b1 treatment and decreased RELN promoter activity in a dose-dependent manner. And we showed that knockdown of Reelin induced the expression of mesenchymal markers and increased cell migration in KYSE510 cells. Our results provide the first evidence linking Reelin to TGF-b signal pathway, which contribute to cancer metastasis, and it is helpful for anti-cancer strategies. a-Synuclein is a small and natively unfolded protein, and it is the first member of synuclein family which is named as earlier studies showed that a-synuclein only localizes in presynaptic terminals and nucleus. Yet later, a-synuclein was shown in the somata of specific neuronal populations in the rat brain, e.g. in the SNpc, using a monoclonal antibody. a-Synuclein has attracted considerable attention due to its involvement in neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Beyond those,Diisopropylammonium dichloroacetate aberrant expression of a-synuclein may be highly associated with human malignancies. However, less is known about its normal function. Several studies already noticed some connection between asynuclein and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a well characterized neurotoxin for inducing PD models at present, which oxidized in vivo into the toxic substrate 1methyl-4-phenylpyridinium. Vila et al. found that MPTP enhances a-synuclein expression in vivo ; Dauer et al. reported that a-synuclein is required for MPTP-induced apoptosis as a-synuclein null mice presents striking resistance to MPTP. These studies established a model to link environmental and genetic factors in PD-like cell death; still, the mechanism underlying is poorly elucidated. Lately, a pathogenic link between a-synuclein and mitochondria was established by the observations that some transgenic mice overexpressing wild-type or mutant a-synuclein develop abnormal mitochondrial morphology.