Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.35 (
matrix metalloproteinase 9
)
2,207
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Recent studies have suggested that loss of
RUNX3
expression is involved with gastric tumor metastasis. However, the precise mechanism of
RUNX3
-mediated suppression of tumor metastasis remains elusive. We aimed to clarify the effect of
RUNX3
on tumor metastasis in gastric cancer cell lines and tumors. Immunohistochemistry revealed that
RUNX3
was significantly decreased in metastatic gastric cancer. Gelatin zymography and Western blot showed that instead of regulating matrix metalloproteinase 9 (MMP9) expression,
RUNX3
expression inhibited
MMP9
enzyme activity, and this was consistent with the upregulation of tissue inhibitor of metalloproteinases 1 (TIMP1) by
RUNX3
. TIMP1 siRNA treatment impaired
RUNX3
-mediated suppression of gastric cancer cell invasion. Reporter assays demonstrated regulation of TIMP-1 by
RUNX3
. Two
RUNX3
binding sites were identified in the TIMP-1 promoter and direct interaction of
RUNX3
with the TIMP-1 promoter was confirmed in vitro and in vivo. These findings provide evidence for
RUNX3
-mediated suppression of gastric cancer invasion and metastasis and define a novel molecular mechanism that for the metastasis-inhibiting activity of
RUNX3
. These data may be applied in the development of
RUNX3
for gastric cancer metastasis diagnostics and therapeutics.
...
PMID:Runx3 suppresses gastric cancer metastasis through inactivation of MMP9 by upregulation of TIMP-1. 2112 46
