Unraveling the role of cellular senescence in cancer
A variety of insults, including oncogenes such as K-Ras, can induce premature cellular senescence. Senescent cells are characterized by an irreversible growth arrest, which is associated with well-defined biochemical alterations. Since senescent cells do not proliferate, cellular senescence is a powerful intrinsic tumor suppressor mechanism.
In fact, oncogene-transformed cells need to escape the senescence barrier to proliferate and progress to higher grades of malignancy. Interestingly, cellular senescence also has pro-tumorigenic properties. For example, senescent stromal cells within the tumor microenvironment develop a senescent-associated secretory phenotype (SASP), a plethora of mostly pro-inflammatory cytokines and chemokines, which can act in a tumor-promoting manner through paracrine mechanisms. Thus, understanding the molecular mechanisms that elicit a senescence response will provide insights into the pathogenesis of cancer and has the potential to impact the development of novel therapeutic interventions.
Ferruccio Galbiati Vice Chair of Research, University of Pittsburgh, Department of Pharmacology & Chemical Biology, will be hosted by Prof. Marco Parenti.