Hallmarks of Cancer 3: Resisting Cell Death
The third Hallmark of Cancer is the cell’s ability to evade apoptosis, otherwise known as cell death. Normally, healthy cells are limited in the number of times it can proceed through division cycles. This limit is controlled by a region located at the end of chromosomes called telomeres. All cells are pre-programmed for apoptosis. It is the cells natural defense system against cancer. When a cell is harmed by an invader or damaged in any way, it can trigger apoptosis and remove itself. When this happens, the cellular membrane, which is like the skin of a cell, breaks apart. Chromosomes, which are condensed and coiled structures of DNA, begins to fall apart. The DNA itself also breaks apart into smaller fragments. As the cell reaches the end of apoptosis, it shrinks and can be incorporated into a neighboring cell or an immune cell. These cells can recycle and reuse parts of the dead cell.
There are two main actors of apoptosis: regulators and effectors. Regulators act as guards of the cell. They observe the internal and external environment and search for anything that might be wrong with the cell. They can then decide whether or not the cell needs to be killed. An example of a regulator are receptors on the cell’s surface that can bind to molecules that signal the cell’s death. Effectors are structures then then act upon the death signal, if given, and break apart the cell.
Several signaling pathways related to apoptosis meet at the mitochondria. The mitochondria is an organelle of the cell and as well known, is the power house of the cell. When a cell becomes cancerous, it interferes with not only normal cellular growth pathways, but also interferes with cellular death pathways. By evading cellular death pathways, the cell is unlimited in the number of times it can divide. There is no control over cell proliferation.
A crucial player of cell division is a protein called retinoblastoma. This protein is an essential block on cell division. It stops the process when necessary, controlling proliferation. However, when there is damage to the gene that codes for the creation of this protein, such as in a cancer cell, the protein cannot be created and the block on cell division is lifted. This leads to uncontrolled proliferation of the cell.
Another crucial player of the cell cycle is the P53 protein that is often called, “The Guardian of the Genome.” This protein can detect any damages in the cell’s DNA or other abnormal features of the chromosomes. If the protein does find something wrong, it can temporarily stop the cell cycle in order to fix the damage. If the damage cannot be undone, then the protein calls for apoptosis to commence. It is common for cancer cells to be missing the P53 protein, often due to damage of its respective gene. The absence of the protein removes the cell’s ability to perform apoptosis and therefore proliferation is no longer controlled.
Having mutations in both the retinoblastoma gene and the P53 gene is often the cause for highly aggressive cancers. These cancers have tumors that grow rapidly as apoptosis is virtually nonexistent and cellular proliferation is under no control.
An example of this Hallmark of Cancer can be seen with prostate cancer. Cancer cells in the prostate undergo uncontrolled cell division and proliferation due to inhibition of apoptosis. For certain types of prostate cancer, an injection treatment called docetaxel can be used. This treatment stops cancer cells from growing and spreading throughout the body.1
1 Gutschner, T., Diederichs, S. The Hallmarks of Cancer. RNA Biology. 2012;9(6):703-719. June 1, 2012.