Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tazarotene-induced gene 1 (TIG1) encodes a protein that is a retinoid-regulated tumor suppressor. TIG1 is expressed in most normal tissues, and downregulation of TIG1 expression in multiple cancers is caused by promoter hypermethylation. Kazal-type serine protease inhibitor-2 (SPINK2) is a serine protease inhibitor, and the SPINK protein family has been shown to inhibit the expression of urokinase-type plasminogen activator (uPA). In addition, increased levels of uPA and the uPA receptor were observed in testicular cancer tissues. This study demonstrated that TIG1 interacts with SPINK2 in NT2/D1 testicular carcinoma cells. TIG1 and SPINK2 were highly expressed in normal testis tissues, while low expression levels of TIG1 and SPINK2 were found in testicular cancer tissues. TIG1 inhibited cell invasion, migration, and epithelial-mesenchymal transition (EMT) of NT2/D1 cells. SPINK2 enhanced TIG1-regulated uPA activity and EMT suppression, while silencing SPINK2 alleviated TIG1-mediated EMT regulation, cell migration, and invasion. Therefore, the results suggest that the interaction between TIG1 and SPINK2 plays an important role in the inhibition of testicular cancer cell EMT, and suppression is mediated through downregulation of the uPA/uPAR signaling pathway.
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PMID:Tazarotene-Induced Gene 1 (TIG1) Interacts with Serine Protease Inhibitor Kazal-Type 2 (SPINK2) to Inhibit Cellular Invasion of Testicular Carcinoma Cells. 3188 33

Tazarotene-induced gene 1 (TIG1) is a retinoid acid receptor-responsive gene involved in cell differentiation and tumorigenesis. Aberrant methylation of CpG islands in the TIG1 promoter is found in multiple cancers. Currently, the exact mechanism underlying the anticancer effect of TIG1 is unknown. Here, we show that TIG1 interacts with cathepsin V (CTSV), which reduces CTSV stability and subsequently affects the production of activated urokinase-type plasminogen activator (uPA), an epithelial-mesenchymal transition-associated protein. Ectopic expression of CTSV increased the expression of activated uPA and the number of migrated and invaded cells, whereas ectopic TIG1 expression reversed the effects of CTSV on the uPA signaling pathway. Similar patterns in the production of activated uPA and number of migrated and invaded cells were also observed in TIG1-expressing and CTSV-knockdown cells. The results suggest that CTSV may participate in TIG1-regulated uPA activity and the associated downstream signaling pathway.
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PMID:Cathepsin V Mediates the Tazarotene-induced Gene 1-induced Reduction in Invasion in Colorectal Cancer Cells. 3291 81