Researchers uncover function of Notch gene in bladder cancer

Researchers part-funded from the European Research Council have made a major discovery on the role of Notch genes and bladder cancer.

Scientists at the Centro Nacional de Investigaciones Oncologicas in Madrid, Spain, have found that the genes exert an anti-tumour effect. This result calls for caution when using therapeutic strategies based on the deactivation of Notch as they could increase the risk of developing bladder cancer. In addition to clarifying the role that Notch plays in bladder cancer, the study authors have also identified clues to understand the dual function of this family of genes.

Writing in The Journal of Clinical Investigation, the research team led by Manuel Serrano and Francisco X Real said: “Our analysis of Notch mutations in bladder cancer, mouse models, cell-based assays and human cancer samples offer solid evidence that the Notch pathway plays a relevant role as a tumour suppressor in bladder cancer.”

Many of the tumours in which Notch act as a suppressor are cancers that arise in squamous cells, which are found in different organs, such as the oesophagus or the skin. The urinary bladder can give rise to squamous cell cancer, so the researchers “hypothesised that Notch could act as a suppressor in this tissue”.

The confirmation of this hypothesis supports the idea that Notch intervenes in the architecture of the so-called ‘stratified epithelia’, in which cells grow in superimposed layers, a type of growth that also takes place in the bladder. Concluding their paper, the scientists said: “Our group, as well as other investigators, had previously described the anti-tumour effects of pharmacologic inhibitors of Notch in pre-clinical models [of lung adenocarcinoma, where Notch is oncogenic]; our current data suggest that caution must be taken in the clinical application of non-specific Notch pathway inhibition, because it could increase the incidence of squamous-type tumours, like in the bladder.”

Notch genes can either be helpful or harmful in the role of promoting or suppressing tumour growth, and consequently such analysis is key in helping to better tackle bladder cancer.