Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although endothelial cell retraction is required before tumor cell invasion, its molecular mechanism still remains obscure. We previously demonstrated that conditioned medium (CM) derived from a human pancreatic cancer cell line, PSN-1, induced endothelial cell retraction and facilitated tumor cell invasion. To investigate the molecular change of events in the transduction of extracellular signals during endothelial cell retraction, we examined the effect of the CM derived from PSN-1 cells on the tyrosine phosphorylation in endothelial cells. Immunoblot analyses revealed that the PSN-1 CM decreased tyrosine phosphorylation of a 120-130 kD protein, and induced the concomitant down-regulation of focal adhesion kinase, pp125FAK, during endothelial cell retraction in time- and dose-dependent fashions. These changes preceded endothelial cell retraction and were reversible after removal of the CM. Further quantitative densitometric analyses demonstrated that the extent of decrease in tyrosine phosphorylated 120-130 kD protein during the endothelial cell retraction was likely to be proportional to that of the down-regulation of pp125FAK. A tyrosine phosphorylated 120-130 kD protein immunoprecipitated by anti-phosphotyrosine antibody immunoreacted with anti-pp125FAK antibody. These results suggested that decreased amount of a tyrosine phosphorylated 120-130 kD protein probably due to the down-regulation of pp125FAK might be associated with the signal transduction pathway in the endothelial cells during their retraction. Furthermore, these findings were also observed in the CM from another four human cancer cell lines, suggesting the down-regulation of pp125FAK in endothelial cells during tumor cell invasion.
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PMID:Down-regulation of focal adhesion kinase, pp125FAK, in endothelial cell retraction during tumor cell invasion. 956 42

Cardiac glycosides are natural compounds used for the treatment of congestive heart failure and cardiac arrhythmias. Recently, they have been reported to exhibit anticancer activity. Proscillaridin A (PSN-A), a cardiac glycoside constituent of Urginea maritima has been shown to exhibit anticancer activity. However, the cellular targets and anticancer mechanism of PSN-A in various cancers including prostate cancer remain largely unexplored. In the present study, we have shown that PSN-A inhibits proliferation and induces apoptosis in prostate cancer cells in a dose-dependent manner. Further mechanistic study have shown that anticancer activity of PSN-A in prostate cancer cells is associated with ROS generation, Bcl-2 family proteins modulation, mitochondrial membrane potential disruption and ultimately activation of caspase-3 and cleavage of PARP. Moreover, we found that PSN-A inhibits JAK2/STAT3 signaling and augments doxorubicin toxicity in prostate cancer cells. Of note, LNCaP cells were found to be more sensitive to PSN-A treatment as compared to DU145 cells. Taken together, the data provided first evidence of the anticancer activity and possible molecular mechanism of PSN-A in prostate cancer. Further study is needed to develop PSN-A into a potential lead compound for the treatment of prostate cancer.
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PMID:Proscillaridin A induces apoptosis, inhibits STAT3 activation and augments doxorubicin toxicity in prostate cancer cells. 3000 94