Description
Ageing and cancer are currently a main concern of the developed countries. Although they are primarily different diseases, they both share a common characteristic - the activation of a cellular phenotype called senescence. Senescence is a cellular response to damage. It is characterised by a cell cycle arrest, the production of various secretion factors and the recruitment of inflammatory cells, resulting in tissue remodelling. However, the precise mechanisms for regulating senescence are not well characterised.
Our lab has identified integrins as regulators of cellular senescence. Integrins are cell surface adhesion receptors formed by an “alpha“ and a “beta” subunit. They identify variations in the extracellular space and mediate intracellular signaling to adapt to changes in the environment. Our lab has characterised how the integrin alpha-v-beta 3 is upregulated during senescence (Figure 1) and induces a TGF-beta rich SASP. Surprisingly, the alpha-v-beta-3 antagonist, cilengitide, prevented the secretion of the SASP, without compromising the proliferative capacity of the senescent cells. Thus, suggesting that cilengitide could be used as an inflammatory chemical with no effect on altering the proliferative effect arrest induced during senescence. Furthermore, the ectopic expression of a vector encoding integrin beta 3 subunit (ITGB3), induces premature senescence in a fashion dependent on the p53/p21CIP pathways. Interestingly, ITGB3 is regulated by the Polycomb Repressive Complex 1 (PRC1) and in particular, the chromobox protein CBX7 regulates this locus during oncogene-induced senescence (by overexpression of H-RasG12V) (Cell Reports 2017, Cell Cycle 2017).
