Mechanisms of Premature Cell Senescence

Cell senescence and malignant transformation are intricately and reciprocally related. The search is on for the ways to induce cancer cell senescence; this explains the growing interest in mechanisms inducing premature cell senescence. Despite many similarities between replicative senescence and stress-induced premature senescence (SIPS), the major distinction between the two lies in the fact that the replicative senescence is almost exclusively associated with the attrition of telomeres, whereas the SIPS is not. In the following pages we shall outline some molecular signatures of SIPS (including Wnt pathway, telomere-independent mechanism driven by a member of polycomb group histone methyltransferase, caveolin-1, sirtuins, and micro-RNA pathways, among others). Further on we shall describe the role of lysosomal dysfunction in the development of SIPS and sirtuin depletion via released cathepsins. The relevance of sirtuins in many cancers is briefly outlined. We summarize the chapter by suggesting several pathways that could be utilized for induction of SIPS in cancer therapy.