A common enzyme, caspase-2 found in mammals that kills damaged cells before they become cancerous is being hailed as an important breakthrough in understanding the treatment of the disease. Researchers from the Centre for Cancer Biology Molecular Regulation Laboratory have found that a deficiency of the caspase-2 enzyme place people at a higher risk of developing tumours.
Caspase-2 is an enzyme associated with apoptosis (cell death) that has now been found to target aneuploid cells, which often develop into tumours if not killed off. Aneuploid cells have been dubbed the hallmark of cancer in about 90 per cent of solid tumours and 85 per cent of hematopoietic neoplasias.
The Molecular Regulation Laboratory research leader Sharad Kumar discovered the caspase-2 enzyme nearly 25 years ago but has only just demonstrated its link to preventing tumours in recent years. In two recent publications, the team demonstrated that cells with a caspase-2 deficiency had weaker apoptosis, the process by which damaged cells are killed off. Some cells that acquired DNA damage or chromosome defects during cell division, survived, due to a block in apoptosis. These surviving cells continued to grow and divide as aneuploid cells. The research also showed that bone marrow cells from mice, which lacked caspase-2, accumulated many of these defective, potentially cancer-causing aneuploid cells with age.
The team's research on caspase-2 deficiency has been recently published in
Cell Death and Disease, Impaired haematopoietic stem cell differentiation and enhanced skewing towards myeloid progenitors in aged caspase-2-deficient mice. 7, e2509; doi:10.1038/cddis.2016.406 (2016) Published online 1 December 2016.
Oncogene, Caspase-2-mediated cell death is required for deleting aneuploid cells. Advance online publication 19 December 2016; doi: 10.1038/onc. 2016.423.