One way that cells die within the body is a process called apoptosis. Apoptosis is a type of cell death that occurs in a series of molecular steps that lead to the death of a cell. During this process, cells undergo programmed cell death. Cells that undergo apoptosis shrink and develop bubble like lumps on their surface. These lumps display a liquid molecule called phosphatidylserine that allows the phagocytes to bind to them. The DNA within the nucleus is broken up into small pieces as well as some the organelles of the cell. The cell then splits up into small chunks and packed neatly enclosed within the membrane. These small pieces let off signals that attract phagocytic immune cells such as macrophages. Apoptosis occurs within the body to remove cells that need to be deleted during development, abnormal cells that could harm the body or cells that need to be removed to maintain homeostasis. Cancer cells thrive within the body because they are able to evade apoptosis. There are two major pathways involved in apoptosis: intrinsic pathway and extrinsic pathway.
Extrinsic Pathway
Extrinsic pathways initiate apoptosis by transmembrane receptor mediated interactions. IN this pathway, death receptors that are apart of tumor necrosis factors that have similar properties of cysteine-rich extracellular domains called death domain. This domain transmits death signals from the cell surface to intracellular pathways. Death receptors bind to cognate ligands and can activate caspases through dimerization controlled by adaptor proteins such as FAS which are associated with death domain protein. Active initiator caspases 8 and 20 cleave and activate effector caspases 3 and 7, resulting in apoptosis.
Intrinsic Pathway
The intrinsic pathway involved the permeability of the mitochondria and release of cytochrome c into the cytoplasm. Cytochrome c then forms multi-protein complex called apoptosome and activates the caspase cascade through caspase 9.From there, caspase caspase 9 activates caspases 3 and 7, leading to apoptosis.
Cancer cells ability to evade the process of apoptosis is a key factor is the progression cancer.
The ability for cancer cells the evade apoptosis is a key factor in the progression of cancer. One of the most important genes in carrying out the process of apoptosis is the p53 gene. Both intrinsic and extrinsic pathways are enhanced by p53. P53 is activated by external and internal stress signals that the pathways send out to promote nuclear accumulation. In most cancer cells, the p53 gene is either missing or has been mutated which causes damage to the function of the p53 gene. Cancer cells cause the loss in function of the p53 gene by increasing inhibitors of the p53 gene or silencing the activators of the p53 gene. By doing so, the damage that is caused by the mutations in the cell cannot be detected by the p53 gene so that they can be repaired. Also, since the p53 gene is no long working properly, it cannot produce the protein Bax, which is a pro-apoptotic protein that induces apoptosis by stimulating the mitochondria to release cytochrome c which activates caspase cascade resulting in cell death.
Since cancer cells have the ability to evade apoptosis, they are able to continue to grow and metastasize.
