Ya’ll know that when you were a fetus you had webbed fingers and toes like a frog, right? Most of us lost that webbing between our fingers by the time we had our birthday. This happens through a process called apoptosis (sounds like A-POP-TOE-SIS). Apoptosis is programmed cell death. It is a nice and tidy process that is hardwired into each cell. When a cell needs to die, apoptosis pathways are activated and the cell commits cellular suicide. When something like toe webbing is supposed to be removed, death signals (I didn’t make that up) from the outside can start the process by engaging death receptors (also not made up) on the cells that make up the webbing of your froggy feet. Likewise, when something is wrong internally in the cell that makes it faulty (like damaged DNA or low oxygen), an internal signal starts the apoptosis process. It is believed that internal pathway is generally more important for removal of cancer cells, but no matter how apoptosis is activated, it is the most pristine crime scene; no trace of the cell is left behind (this is opposed to necrosis which is hot mess…but that comes later). Obviously, cancer cells are full of bad things and the cell should recognize those bad things and activate apoptosis pathways to remove it, but….yep, Cancer Hallmark #3 is….drumroll…RESISTING CELL DEATH (APOPTOSIS).
So, how do our sneaky cancer cells rise up in resistance? The most common way is to mutate or lose the gene that is responsible for production of a very important protein called P53. P53 is dubbed the “guardian of the genome” and half of all cancers have something wrong with this gene and the subsequent protein. One of P53’s most important functions is to act as a gatekeeper of apoptosis and start the internal apoptosis process. However, when a cancer cell has defective version of P53, then its role as apoptosis gatekeeper is lost and the cell is able to resist death despite being completely messed up.
Here is a quick recap of Hallmarks #1-3.
1. The ‘grow’ switch is stuck ON and cells are growing and dividing
2. The brakes are not working and cells divide out of control
3. The out of control cancer cells resist death
#morethanfour #ChildhoodCancer365
Header graphic from (which is an excellent article on p53 from an epidemiology perspective) : https://mosaicscience.com/story/brazils-cancer-curse/
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