Abstract
Cellular senescence is activated by numerous cellular insults, in particular those driving cancer formation, resulting in stable proliferation arrest and acquisition of specific features. By self-opposing to oncogenic stimulation, senescence is considered as a failsafe program, allowing, when functional, to inhibit cancers occurrence. Compelling evidences suggest a tumor suppressive activity of caspase-2, eventually independently of its effect on cell death. The original results described here demonstrate that this tumor suppressive activity of caspase-2 is mediated, at least in part, by its pro-senescing activity. Indeed, we have demonstrated in vitro and in vivo that loss of function of caspase-2 allows to escape oncogenic stress induced senescence. These results are discussed in the context of known tumor suppressive activity of caspase-2.
Highlights
Caspase-2 is the most evolutionarily conserved of all the caspases
During cell cycle arrest caused by tumor suppressors, mitogenic signaling like Ras and mTOR drive conversion of cell cycle arrest to senescence [5]
The mechanisms involved in oncogene-induced senescence escape are still unclear, especially in epithelial cells [6]
Summary
Caspase-2 is the most evolutionarily conserved of all the caspases. the caspase-2 knockout mice do not display major alteration and its role in apoptosis remains discussed [1]. Caspase-2 is regulating proliferation and transformation showing a role beyond apoptosis regulation. During these last years compelling evidence support an important tumor suppressive role of the caspase-2. The loss of caspase-2 cooperates with Ras to transform mouse embryonic fibroblasts [2], with myc to favor lymphomagenesis [2, 3], or with neu to favor mammary tumorigenesis [4].
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