Senescence: protecting us from all the wrong things
Senescence was first defined as the irreversible growth arrest suffered by primary cells when they reach the end of their replicative potential. Interestingly, a kind of senescecne triggered by oncogene activation, termed OIS (oncogene-induced senescence) has been show to limit cancer progression by engaging the p16/Rb and the p53 tumor suppressor pathways. In the first part of the talk, I will present how we can exploit bypass of senescence genetic screens to identify novel regulators of senescence and eventually identify their role in cancer.By doing bypass of senescence screens, we unveiled that chemokine signalling via the CXCR2 receptor is upregulated during senescence and contributes to reinforce growth arrest. Potentially, activation of CXCR2 can have tumor suppressor properties early in tumorigenesis.
We have also identified a histone demethylase, JMJD3 that is a critical mediator in the activation of the Ink4a/Arf locus in response to Ras.
In the final part of the talk, we will present evidence that senescence can be also triggered by other stresses, such as reprogramming to induced pluripotent stem cells (iPS). The implication of this observation is that by inhibiting senescence, the efficiency of iPS generation can be vastly improve. However, our results also highlight the uncanning similarities between the acquisition of pluripotency and cancer progression, and make us wonder how to not only improve the efficiency of generation of iPS, but also make it safer.
Forum HZI, X1.04
Jesús Gil, Imperial College, Faculty of Medicine, Hammersmith Hospital, London
Prof. Dr. Lars Zender