Abstract:
The cellular senescence pathway is a stress response pathway involved in limiting the proliferation of cells that are at risk of becoming cancerous. Tumour suppressor genes of the cells get activated during senescence induction to deactivate cell cycle proteins and enter a state of growth arrest, and at the same time, cells show hyperfunction, which results in the cell-type dependent secretion of pro-inflammatory cytokines and altered tissue microenvironments. Cellular senescence can be induced by a number of methods such as gamma irradiation, treatment with chemotherapeutic or DNA damage agents and telomere shortening due to repeated replication. The nuclear architecture of senescent cells has common features and deformations compared to both normal aging cells and premature aging models such as Hutchinson-Gilford progeria syndrome (HGPS) [Yoon et al., 2019]. Our experiments involve inducing and characterising senescence in cell lines using etoposide, a well-known chemotherapeutic agent used to treat cancers. The gene expression status of lamins and LINC complex proteins is analyzed after etoposide treatment and with serum starvation. While cellular senescence is classically thought to be a permanent state of cell cycle arrest, tumour cell escape from senescence has also been observed [Saleh et al., 2019]. This is a cause for concern since senescence reversal can promote cancer relapse, and shows the complex ways in which senescence may affect in vivo cancer progression and tissue remodelling. Our studies aim to elucidate the role of lamins and the LINC complex in the senescence mechanism in order to find specific biomarkers of senescence and better avenues in cancer therapy and senolytics.
