New signaling pathway in cancer and aging

A new study shows how a key protein in cancer and aging, PI3K, modulates the protection of telomeres by acting on TRF1, telosomes essential for the integrity of telomeres. Inhibition of PI3K causes the decrease of TRF1 levels and the destabilization of chromosomes. This finding is a new target to attack telomeres, which in the absence of drugs that destroy them, have the ability that cancer cells can divide uncontrollably.

The researchers hypothesized that the decrease in TRF1 was due to the action of PI3K, since the compounds used belong to a series previously identified as inhibitors of PI3K. When administering these compounds, they observed that the levels of TRF1 diminished and, in addition, the action of PI3K was inhibited, but they did not know if there was a connection and what it could be. Here comes another of the components of the PI3K pathway called AKT, which was found to effectively modify TRF1 by phosphorylation. By blocking PI3K, these phosphorylation reactions are blocked and TRF1 loses stability, has a shorter half-life and binds less to the telomere, deprotecting it.

Scientists have found in PDX mice (in which a tumor derived from a patient is grown to check the effectiveness of different therapies) that the response to treatment with these PI3K inhibitors is related to the decrease in TRF1 levels. The study was published in Nat Commun. December 12/2017 (neurologia.com)

Source: Al Dia. Infomed

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