PI3-K/AKT Regulation of NF-κB Signaling Events in Suppression of TNF-Induced Apoptosis

Melanoma cell migration to type IV collagen requires activation of NF-κB

“…Furthermore, dominant negative Rac or Ras expression results in a modest reduction of CIV-induced NF-kB binding activity. PI-3K has also been shown to play a role in inducing NF-kB, by regulating Akt/PKB activity (Burow et al, 2000;Rong et al, 2002), and our preliminary data suggest that PI-3K influences NF-kB activity as well as cell migration (data not shown). Therefore, NF-kB is a likely target of integrin-mediated signaling pathways.…”

Distinctive role of integrin-mediated adhesion in TNF-induced PKB/Akt and NF-κB activation and endothelial cell survival

“…Here we demonstrate that concomitant activation of PKB/Akt and NF-kB is necessary for the survival of endothelial cells exposed to TNF, implicating that in HUVEC these pathways are independently activated by TNF and elicit non-redundant survival responses. This was not an anticipated result, because in breast cancer cells inhibition of PKB/ Akt enhanced TNF toxicity indirectly by attenuating NF-kB activation (Burow et al, 2000), whereas hepatocytes resist to TNF-induced death with just one pathway active (Imose et al, 2003). b1 integrinmediated adhesion protects aggressive prostate cancer cells against anoikis or TNF via PKB/Akt-dependent upregulation of survivin (Fornaro et al, 2003).…”

“…Protein kinase B (PKB), also known as Akt, is a serine-threonine kinase activated by growth factor and adhesion receptors playing a critical role in promoting adhesion-dependent endothelial cell survival (Khwaja et al, 1997). TNF can activate PKB/Akt to promote protein synthesis and cell survival (Burow et al, 2000).…”

Expression of the NF-κB Target Gene X-Ray-Inducible Immediate Early Response Factor-1 Short Enhances TNF-α-Induced Hepatocyte Apoptosis by Inhibiting Akt Activation

“…Thus, it may be reasonable to speculate that the proapoptotic effect of IEX-1S is mediated by the inhibition of antiapoptotic signal(s) activated by TNF-␣. In several types of cells such as HeLa cells and human endothelial cells, TNF-␣ appears to activate serine/threonine kinase Akt via PI3K (28, 34 -36), which protects cells from apoptosis (28,29,36,37). In hepatocytes, TNF-␣ activates the PI3K/Akt pathway which inhibits apoptosis mediated by TNF-␣ and this protective effect is independent of NF-B (8).…”