Cell survival pathways

PTEN interactions with FAK, and that PTEN regulates FAK phosphorylation and molecular associations after detachment from matrix, suggesting that PTEN negatively regulates the extracellular matrix-dependent PI3-K/Akt cell survival pathway in a process that can include FAK (Tamura et al, 1999). 

Tamura, M., Gu, J., Danen, E.H., Takino, T., Miyamoto, S., Yamada, KM., 1999, PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidyhnositol 3-kinase/Akt cell survival pathway. JBiol Chem 274 ... 

Tumour cells use multiple cell survival pathways to prevail, and thus the ter-penes that can suppress multiple pathways have great potential for the treatment of cancer. This review presents evidence that terpenes can be used not only for cancer prevention but also for its treatment. 

Figure 15.4 Mechanisms of apoptosis induction by resveratrol. Resveratrol selectively induces apoptosis in various cancer cells in culture by several mechanisms including activation of death receptor-mediated signaling, mitochondria-dependent cytochrome c release and caspase activation, induction of p53 and p53-regulated proapototic genes, activation of MAP kinase-mediated p53 phosphorylation, blockade of Akt-mediated cell survival pathways, and accumulation of intracellular ceramide level.

It should be noted that agonists of PLD simulate the effects of IP, whereas the inhibition of PLD blocks the beneficial effects of IP (Ozer et al., 2005 Hashizume et al., 1997). In summary, the two extremes of stress imposed on the heart under I-R change the redox potential of the cardiomyocyte and affect redox-sensitive molecules involved in phospholipid-mediated signal transduction mechanisms. The early activation of specific PLC and PLD isozymes may represent initiation of redox signaling and cell survival pathways, whereas inactivation of specific PLC and PLD isozymes may contribute to impaired cardiac contractile function (Fig. 11.6). 

Initiation of redox signaling and cell survival pathways... 

C and activation of caspase-9 and caspase-3. " More recently, we have demonstrated that curcumin can suppress the proliferation of multiple myeloma cells. Woo et al. have demonstrated that curcumin can cause cell damage by inactivating the Akt-related cell survival pathway and release of cytochrome c, providing a new mechanism for curcumin-induced cytotoxicity. 

The ancient JAK/STAT/MAPK complex serves as a cell survival pathway , when temporarily activated the constitutively activated pathway transforms the cell to immortality, with the eventual demise of its host. However, small molecular inhibitors already exist (vide supra), that may reverse the oncogenic process the constitutively activated oncogene or its oncoprotein (including the overproduction of type I IFNs) may be de-activated (vide infra). 

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