Death is just as important as life when shaping complex organisms. In the life of a multi-cellular creature like Homo Sapiens, single-cell life and death complete each other like a molecular Yin and Yang. The gaps in between your fingers used to be filled with tissue, before they were precisely and almost surgically killed off by the development blueprint of the embryo. In fully grown adults, old cells are often a liability because they are more subject to mutation and therefore are at increased risk of forming a tumor. As a preventive measure, most cell types are efficiently killed off after a certain period of time, when fresh substitute cells are ready to take their place. This form of tightly controlled, mechanically regulated death is known as apoptosis. The word apoptosis comes from the ancient Greek and means “to fall off”, which is pretty much what happens when cells die and become discarded by the organism.
Apoptosis is very tightly regulated by a network of molecular pathways that make sure it only occurs at the right time and in response to the right signals. For example, cells in the human body benefit from a mutation-detecting mechanism. If a mutation in the cell’s DNA is detected and cannot be fixed, the cell initiates a “self-destruction protocol” that quickly leads to apoptosis. In order for a cancer to develop, healthy cells need to acquire the ability to go around this fail-safe mechanism. Once they do, they can begin accumulating mutations in different genes, which eventually leads to the formation of a tumor. Cancer cells can collect all the mutations they require through all the key Hallmarks to form a real malignancy.
The way cells go around the fail-safe mechanism is usually through mutations in specific genes that drive apoptosis or recognize mutation. The most notorious example in this case is mutations in the p53 gene, which are found in all the most common types of cancer. In a healthy cell, p53 promotes the production of a protein known as PUMA, which is an essential clog in the machine of apoptosis. When p53 is mutated and cannot function properly, it won’t activate the cell-death machine and therefore more mutations can accumulate and eventually lead to cancer.
A lot of very exciting cancer research over the last ten years has focused on how to induce apoptosis in cells. While there is a lot of work yet to be done to completely understand this process and to exploit to treat patients, there have been many promising ideas in the field.
This post is the second in the series “Understanding cancer”. Please go check out the rest of the posts here.