Deciphering Oncogene and Therapy-induced Senescencefor new Therapeutic Strategies

Tarih: 15.01.2016
Yer: Boğaziçi Üniversitesi KP 315 (Seminar Room)

Deciphering Oncogene and Therapy-induced Senescencefor new Therapeutic Strategies

Müge Öğrünç, Ph.D.
INSERM Paris
 
Oncogenes are the mutated forms of cellular genes that are responsible for driving rampant cellular proliferation. Oncogene activation is a key step in cellular transformation and cancer maintenance. However, the expression of an activated oncogene in normal human cells does not lead to their transformation, but to a permanent cell-cycle arrest known as cellular senescence. The discovery of oncogene-induced cellular senescence (OIS) suggests that cell-intrinsic mechanisms respond to oncogene activation by the enforcement of cellular senescence as tumour suppressor. We showed that oncogene-induced reactive oxygen species (ROS) are essential for oncogene-driven hyperproliferation. ROS, as modulators of cell hyperproliferation, is a novel concept based on the analysis of several consistent results obtained in various experimental set ups that will be presented. Though multiple stress signals operate via distinct signalling pathways for the establishment of senescence, oncogenic stimuli interestingly seem to coordinate several major tumour suppressor networks via promyelocytic leukemia protein (PML) nuclear bodies (NBs). In strong support of this notion, we recently demonstrated that upon targeted therapy, loss of self-renewal of leukemia-initiating cells in acute promyelocytic leukemia depends on both intact PML and P53 leading to therapy-induced senescence. I found that PML coordinates P53 post-translational modifications yielding to activation of a distinct set of senescence-associated genes. The efficacy of a simple cascade of events leading to senescence opens prospects for harnessing this PML/P53 pathway in other types of cancers, in addition to engaging such studies concerning senescence a nascent yet promising field of investigation.
 
Date  :  Friday, January 15, 2016
Time :  15.00
Place :  KP 315 (Seminar Room)