Cellular senescence in cancer and ageing

Senescent cells cease to proliferate. The stability of this cell cycle arrest is critical for the tumour suppressive role of senescence, as some senescent cells persist within tissues for long periods (e.g. Naevi are benign tumours that cease proliferating, due to senescence arrest). However, not all senescent cells persist, but if they do, they can be harmful.

Senescent cells are not inert, but rather actively communicate with their surroundings, influencing the microenvironment and potentially burdening the tissue.  Hence senescent cells can also be cleared from the tissue, typically via activating an immune response. An imperfect clearance of senescent cells from the tissue microenvironment may promote cancer and degenerative disorders.

Key questions:

  1. How gene expression is regulated during senescence, compared with other stress responses
  2. How cell communication modulates senescence-associated phenotypes
  3. How senescence modulates tumour initiation
  4. How ageing contributes to tumorigenesis

And:

5. Why benign tumours are benign?

Key effectors/pathways:  Chromatin and nuclear structure, NOTCH signalling, Autophagy, p53 – and any novel effectors