Relationship between chromosomal instability and senescence revealed in the fly Drosophila

Chromosomal instability is a hallmark of solid tumours like carcinoma. Cellular senescence, which is closely linked to cellular ageing, is also a feature of solid tumours like carcinoma. It is also becoming more apparent that it is linked to cancer. Marco Miln, an ICREA researcher, and his team at IRB Barcelona discovered the connection between chromosomal instability (chromosomal instability) and cellular senescence."Chromosomal instability (senescence) are two common characteristics of most cancers. However, it wasn't known how they related. "Our studies suggest that senescence might be one of the intermediate connections between chromosomal changes and cancer," Dr. Milan, who heads the Development and Growth Control laboratory of IRB Barcelona."The behavior we observed in cells with chromosomal instability led us to believe that these cells could be senescent, and that is what it was!" Dr. Jery Joy was the first to publish the article in Developmental Cell.This study was conducted on Drosophila fly, a common animal model used in biomedicine. The mechanisms described could help to understand the role of chromosomal instability (and senescence) to cancer and aid in the identification of potential therapeutic targets.Reversing the consequences of chromosomal instabilityResearchers from the Development and Growth Control laboratory have demonstrated that cells with a low level of chromosomal stability in epithelial tissue can become senescent and detach themselves from their neighbors. Senescent cells exhibit a halt in cell cycle and the secretion a large amount of proteins. The abnormal production of proteins can cause inflammation and alert the immune system.The body must eliminate senescent cells immediately to prevent them from growing into malignant tumours. Dr. Milan says, "If we find the mechanisms that we can reduce the number of senescent cell count, then we'll be able to decrease the growth of these tumors." Dr. Joy says that the study actually shows this is possible in Drosophila.Unbalanced chromosomes cause cells to accumulate high numbers of aberrant mitochondria, which causes a high level oxidative stress. This activates the JNK signalling pathway and triggers senescence. Dr. Joy reiterates that it is possible to reduce the high number of mitochondria or regulate the oxidative stress they cause, which can decrease the number and negative effects of chromosomal instability.These discoveries open up new research avenues to discover therapeutic targets and decrease senescence caused by chromosomal instability of solid tumours.Extrapolating from the fly into mammalsBiomedicine is widely used by the vinegar fly Drosophila melanogaster. Because of its short lifespan, availability of many genetic tools and presence of the same genes in humans but with lower levels of redundancy, it is an excellent animal model for cancer research.This model organism allows for more efficient analysis of experiments that seek to determine the causal relationship between cell behaviour and characteristics in human tumors.Future laboratory research will continue to investigate the molecular mechanisms that govern cell behaviours in epithelial solid tumours. Dr. Milan concludes that the more we know about the biology of the tissue and the molecular mechanisms that cause malignant tumours to form, the better our chances are of developing effective treatments and reducing human cancer's growth and malignancy.###The Ministry of Science and Innovation and ERDF funded this work.