Attenuation of TORC1 signaling delays replicative and oncogenic RAS-induced senescence.

ABSTRACT: Numerous stimuli, including oncogenic signaling, DNA damage or eroded telomeres trigger proliferative arrest, termed cellular senescence. Accumulating evidence suggests that cellular senescence is a potent barrier to tumorigenesis in vivo, however oncogene induced senescence can also promote cellular transformation. Several oncogenes, whose overexpression results in cellular senescence, converge on the TOR (target of rapamycin) pathway. We therefore examined whether attenuation of TOR results in delay or reversal of cellular senescence. By using primary human fibroblasts undergoing either replicative or oncogenic RAS-induced senescence, we demonstrated that senescence can be delayed, and some aspects of senescence can be reversed by inhibition of TOR, using either the TOR inhibitor rapamyc

SUBMITTER: Kolesnichenko M 

PROVIDER: S-EPMC3383597 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature