Role of Notch signalling pathway in cancer and its association with DNA methylation

Abstract

The Notch signalling pathway is an evolutionarily conserved cell signalling pathway involved in the development of organisms as diverse as humans and fruit flies. It plays a pivotal role in cell fate determination. Dysregulated Notch signalling is oncogenic, inhibits apoptosis and promotes cell survival. Abnormal Notch signalling is seen in many cancers like T-cell acute lymphoblastic leukaemia, acute myeloid leukaemia and cancers of the breast, cervix, colon, pancreas, skin and brain. Inhibition of Notch signalling leads to growth arrest and differentiation in those cells in which Notch pathway is activated and this represents a new target for cancer therapy. Cancer develops from genome defects, including both genetic and epigenetic alterations. Epigenetics deals with heritable changes in gene function that occur without a change in the DNA sequence. Among various epigenetic alterations such as acetylation, phosphorylation, ubiquitylation and sumoylation, promoter region methylation is considered as an important component in cancer development. Epigenetic alterations can be used as biomarkers in screening, detection, diagnosis, staging and risk stratification of various cancers. DNA methylation can be therapeutically reversed and demethylating drugs have proven to be promising in cancer treatment. This review focusses on the methylation status of genes in Notch signalling pathway from various cancers and how this epigenetic alteration can be used as a biomarker for cancer diagnosis and subsequent treatment.