Anti-SLC6A3 (extracellular domain) polyclonal antibody

Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator in response to hypoxia and its transcriptional activity is crucial for cancer cell mobility. Here we present evidence for a novel epigenetic mechanism that regulates HIF-1 transcriptional activity and HIF-1-dependent migration of glioblastoma cells. The lysine methyltransferases G9a and GLP directly bound to the alpha subunit of HIF-1 (HIF-1 alpha) and catalyzed mono- and di-methylation of HIF-1 alpha at lysine (K) 674 in vitro and in vivo. K674 methylation suppressed HIF-1 transcriptional activity and expression of its downstream target genes PTGS1, NDNF, SLC6A3, and Linc01132 in human glioblastoma U251MG cells. Inhibition of HIF-1 by K674 methylation is due to reduced HIF-1 alpha transactivation domain function but not increased HIF-1 alpha protein degradation or impaired binding of HIF-1 to hypoxia response elements. K674 methylation significantly decreased HIF-1-dependent migration of U251MG cells under hypoxia. Importantly, we found that G9a was downregulated by hypoxia in glioblastoma, which was inversely correlated with PTGS1 expression and survival of patients with glioblastoma. Therefore, our findings uncover a hypoxia-induced negative feedback mechanism that maintains high activity of HIF-1 and cell mobility in human glioblastoma.

Critical roles of epigenomic alterations in the pathogenesis of breast cancer have recently seized great attentions toward finding epimarkers in either non-invasive or semi-non-invasive samples as well as peripheral blood. In this way, methylated DNA immunoprecipitation microarray (MeDIP-chip) was performed on DNA samples isolated from white blood cells of 30 breast cancer patients compared to 30 healthy controls. A total of 1799 differentially methylated regions were identified including SLC6A3, Rab40C, ZNF584, and FOXD3 whose significant methylation differences were confirmed in breast cancer patients through quantitative real-time polymerase chain reaction. Hypermethylation of APC, HDAC1, and GSK1 genes has been previously reported in more than one study on tissue samples of breast cancer. Methylation of those aforementioned genes in white blood cells of our young patients not only relies on their importance in breast cancer pathogenesis but also may highlight their potential as early epimarkers that makes further assessments necessary in large cohort studies.