Marco Milán

Institut de Recerca Biomèdica

Chromosomal instability (CIN), the continuous change in chromosome number and structure, is a
feature of most solid tumours. Likewise, cellular senescence is a process that is highly related to
cellular ageing and its link to cancer is becoming increasingly clear. The work carried out by Jery Joy
and colleagues in the laboratory of Marco Milán has utilized Drosophila as model system to show that
in an epithelial tissue with high levels of CIN those cells with an altered balance of chromosome
number detach from their neighbouring cells and enter senescence. Senescent cells are
characterised by a permanently halted cell cycle and by the secretion of a large number of proteins.

This abnormal secretion of proteins alters the surrounding tissue, alerting the immune system and
causing inflammation. Cells with an unbalanced number of chromosomes present high levels of
proteotoxic stress, accumulate aberrant mitochondria and, therefore, a high level of oxidative stress,
which in turn activates the c-Jun N-terminal kinase (JNK) signalling pathway, triggering entry into

Interestingly, removing dysfunctional mitochondria or reducing proteotoxic stress by
different means rescue the deleterious effects of CIN. These findings open new avenues of research
to find therapeutic targets and reduce senescence levels caused by chromosomal instability in solid