Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD6 is a 130 000 MW T-cell surface glycoprotein that can deliver coactivating signals to mature T lymphocytes. Studies using monoclonal antibodies (mAb) have defined at least four epitopes on CD6, and distinct functional responses are elicited by mAb to the different epitopes. The function of CD6 is unknown. Multiple CD6 ligands are predicted, based on data that a soluble CD6 fusion protein precipitates at least three peptides. A cDNA clone for one of these ligands, termed activated leucocyte-cell adhesion molecule (ALCAM) has recently been isolated. In order to further characterize the role of CD6 in cell-cell interactions, we have examined the role of CD6 in a variety of responses by tetanus toxoid (TT) specific human T-cell clones. Anti-CD6 mAb UMCD6 (epitope 3) inhibits antigen-specific responses of such clones to TT, but not to the superantigen SEA. Responses of clones to nominal antigen are CD6-dependent using either peripheral blood mononuclear cells (PBMC) or macrophage-depleted E rosette negative cells as the antigen-presenting cell (APC) population. Furthermore, these clones made autoreactive with DNA methyltransferase inhibitors express increased CD6, and autoreactivity is inhibited by UMCD6. Taken together, the data suggests the existence of a functional CD6 ligand in peripheral blood which is expressed by APC, including cells other than macrophages. Interactions between CD6 and CD6 ligands may regulate both antigen specific and autoreactive responses of human T lymphocytes.
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PMID:Role of the CD6 glycoprotein in antigen-specific and autoreactive responses of cloned human T lymphocytes. 888 54

Metastasis-mediated death remains a major challenge in cancer treatment due to the lack of identifiable biomarkers for early diagnosis. Identifying tumor-specific biomarkers is critical for the development of diagnostic and therapeutic tools. In the present study, we found that podocalyxin-like 1 (PODXL), a cell surface glycoprotein, was overexpressed in cancer tissues and was upregulated in lymph node metastatic tumor cells. The expression of PODXL was associated with the migratory ability of human oral squamous cell carcinoma (OSCC). Knockdown of PODXL by small hairpin RNA in the SAS OSCC cell line reduced tumor migration and invasion, and inhibited cell proliferation and colony formation. Suppression of PODXL resulted in downregulation of focal adhesion kinase (FAK) and paxillin phosphorylation. PODXL silencing inhibited filopodia formation, and suppressed F-actin and cortactin colocalization. In addition, PODXL expression was associated with the DNA methylation status, and treatment with the DNA methyltransferase inhibitor 5-aza-deoxycytidine increased the PODXL transcriptional level. Moreover, DNA microarray analysis data revealed that suppression of PODXL significantly affected subsets of genes associated with extracellular matrix organization, the epithelial-mesenchymal transition, and the expression of metastasis-related cytokines. Collectively, these data showed that the overexpression of PODXL may be associated with tumor aggressiveness and that PODXL could be a diagnostic biomarker for metastatic OSCC.
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PMID:Podocalyxin-like 1 is associated with tumor aggressiveness and metastatic gene expression in human oral squamous cell carcinoma. 2482 9

The systemic and resistant nature of metastatic neuroblastoma renders it largely incurable with current multimodal treatment. Clinical progression stems mainly from the increasing burden of metastatic colonization. Therapeutically inhibiting the migration-invasion-metastasis cascade would be of great benefit, but the mechanisms driving this cycle are as yet poorly understood. In-depth transcriptome analyses and ChIP-qPCR identified the cell surface glycoprotein, CD9, as a major downstream player and direct target of the recently described GRHL1 tumor suppressor. CD9 is known to block or facilitate cancer cell motility and metastasis dependent upon entity. High-level CD9 expression in primary neuroblastomas correlated with patient survival and established markers for favorable disease. Low-level CD9 expression was an independent risk factor for adverse outcome. MYCN and HDAC5 colocalized to the CD9 promoter and repressed transcription. CD9 expression diminished with progressive tumor development in the TH-MYCN transgenic mouse model for neuroblastoma, and CD9 expression in neuroblastic tumors was far below that in ganglia from wildtype mice. Primary neuroblastomas lacking MYCN amplifications displayed differential CD9 promoter methylation in methyl-CpG-binding domain sequencing analyses, and high-level methylation was associated with advanced stage disease, supporting epigenetic regulation. Inducing CD9 expression in a SH-EP cell model inhibited migration and invasion in Boyden chamber assays. Enforced CD9 expression in neuroblastoma cells transplanted onto chicken chorioallantoic membranes strongly reduced metastasis to embryonic bone marrow. Combined treatment of neuroblastoma cells with HDAC/DNA methyltransferase inhibitors synergistically induced CD9 expression despite hypoxic, metabolic or cytotoxic stress. Our results show CD9 is a critical and indirectly druggable suppressor of the invasion-metastasis cycle in neuroblastoma.
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PMID:MYCN and HDAC5 transcriptionally repress CD9 to trigger invasion and metastasis in neuroblastoma. 2757 23