Mammals have eight distinct isoforms of phosphatidylinositol 3-kinases (PI3Ks), families of enzymes involved in cellular functions such as cell growth, proliferation, differentiation and survival, and intracellular trafficking. One of the key PI3K isoforms in cancer is p110a, as this isoform is extremely frequently activated by mutation. 'The role of p110alpha isoform of PI 3-kinase in oncogenesis and cellular senescence' (PI3K/oncogenesis) project is investigating how p110a achieves this function with the aim of better understanding the role of this isoform in human cancer. Partners believe that this knowledge will aid the development of rational therapies for the treatment of cancers in which PI3K is over-activated. They are therefore especially keen to determine whether the inhibition of multiple PI3K isoforms is essential to block cell proliferation and survival. Within the first seven months, the researchers in the UK made the discovery that the loss-of-function of p110a leads to a peculiar form of cell senescence, whereby normal diploid cells lose the ability to divide. The researchers now want to follow up this finding by further dissecting the underlying signalling mechanisms of this process.
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