Amongst all the molecules participating in these events, vascular endothelial growth factor is particularly relevant because it modulates the function www.selleckchem.com/products/Calcitriol-(Rocaltrol).html of vascular and non vascular cells, and promotes every step of angiogenesis, in both physiological and pathological conditions. In tumors, the inhibitor of apoptosis protein sur vivin has been ascribed highly pleiotropic functions and is associated with tumor progression, metastasis and angiogenesis. Importantly, survivin is overexpressed in essentially all human cancers and generally absent in normal adult Inhibitors,Modulators,Libraries tissues. As part of the chromosomal passenger complex, crucial for mitosis, survivin facili tates proliferation. Also, as an IAP, this protein is im plicated in the inhibition of apoptosis, although the mechanism by which this is achieved remains a matter of debate.

Some possibilities include interaction and stabilization of the anti apoptotic proteins XIAP or HBXIP and inhibition of pro apoptotic proteins like second mitochondria Inhibitors,Modulators,Libraries derived activator of caspases direct inhibitor of apoptosis binding protein with low pI or Apoptosis Inducing Factor. More recently survivin has been shown to promote invasion and metastasis by enhancing Nuclear Factor kappa light chain enhancer of activated B cells dependent transcription of fibronectin. Survivin has also been shown to promote survival of endothelial cells, EC proliferation and angiogenesis, an expected finding given that proliferating EC need to upregulate survivin.

Rather intriguingly, down regulation of survivin in tumor cells and not in the EC was also shown to reduce angiogenesis in gastric cancer cell lines suggesting that survivin may regulate angiogenesis not only by controlling EC proliferation, but also Inhibitors,Modulators,Libraries via mechanisms occurring in the tumor cells that enhance angiogenesis. These Inhibitors,Modulators,Libraries findings have been examined in human breast cancer and cervical cancer cell lines, and more recently, survivin was shown to favor angiogenesis by enhancing secretion of VEGF. Thus, despite clearly being relevant to the process Inhibitors,Modulators,Libraries of angiogenesis, the mechanisms by which survivin expression in tumor cells favors this process remain poorly defined. Survivin expression is regulated by transcriptional and posttranslational events. Transcription factors implicated in controlling survivin expression include Hypoxia Inducible Factor 1, NF��B, Signal Transducer and Activator of Transcription 3, Notch and B catenin TcfLef.

The B catenin TcfLef is one of the most studied path ways involved in regulating survivin. Although initially described in drosophila development, the Wnt B catenin signaling pathway was rapidly selleckchem Wortmannin recognized to play a critical role in human cancer. For instance, the adenomatous poliposis coli protein is part of the complex involved in B catenin degradation and APC mutations or deletions are known causes of heredi tary colon cancer.