Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the expression of the metastases-associated gene MTA1 correlates with tumor metastases, its role in regulating type IV collagenase expression is unknown. Enforced MTA1 expression in HT1080 cells reduced basal and 12-myristate 13-acetate-induced 92-kDa type IV collagenase (MMP-9) protein/mRNA levels. DNase I hypersensitivity and PstI accessibility assays revealed multiple regions of the MMP-9 promoter (-650/-450 and -120/+1), showing reduced hypersensitivity in the MTA1-expressing cells. Chromatin immunoprecipitation assays demonstrated MTA1 binding to the distal region, which spans several regulatory cis elements. Co-immunoprecipitation and chromatin immunoprecipitation assay experiments revealed histone deacetylase 2 (HDAC2)-MTA1 protein-protein interactions and the MTA1-dependent recruitment of HDAC2 to the distal MMP-9 promoter region, yielding diminished histone H3/H4 acetylation. However, HDAC2 binding and H3/H4 acetylation at the proximal MMP-9 region were unaffected by MTA1 expression. Furthermore, trichostatin treatment only partially relieved MTA1-repressed MMP-9 expression, indicating a HDAC-insensitive component possibly involv ing the nucleosome-remodeling Mi2 activity, which was recruited to the promoter by MTA1. In summary, (a) MMP-9 adds to a short list of MTA1-regulated genes, which so far only includes c-myc and pS2, and (b) MTA1 binds to the MMP-9 promoter, thereby repressing expression of this type IV collagenase via histone-dependent and independent mechanisms.
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PMID:Repression of 92-kDa type IV collagenase expression by MTA1 is mediated through direct interactions with the promoter via a mechanism, which is both dependent on and independent of histone deacetylation. 1243 81

Gastrokine-2 (GKN2) is a secretory protein that is decreased or absent in gastric cancer tissues. In addition, it is reported that trefoil factor 1 (TFF1) and TFF2 can both bind GKN2. In this study, we investigated the expression and biological functions of GKN2 and its interaction with TFF2 in gastric cancer. We found that GKN2 expression was significantly downregulated or absent in gastric cancer cell lines, gastric intestinal metaplasia, and tumor tissues. Overexpression of GKN2 suppressed the proliferation, migration, and invasion of gastric cancer cells and arrested the cell cycle at the G1-S transition phase. Furthermore, GKN2 efficiently attenuated tumor growth in SGC-7901 nude mice xenograft models. Overexpression of GKN2 also reduced the expression levels of cylinD1, cyclinE1, and matrix metalloproteinase 9 (MMP9), which were correlated with proliferation and metastasis of cancer cells. In co-transfected cells, TFF2 and GKN2 did not bind to each other. Overexpression of both GKN2 and TFF2 showed the same inhibitory effect as overexpression of GKN2 alone. Taken together, these findings suggested that GKN2 could inhibit the proliferation, migration, and invasion of gastric cancer cells and might represent a novel therapeutic target for gastric cancer. TFF2 may not interact or cooperate with GKN2, either structurally or functionally.
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PMID:Gastrokine-2 is downregulated in gastric cancer and its restoration suppresses gastric tumorigenesis and cancer metastasis. 2440 14