Who is ready for Hallmark #2 of cancer? Hallmark #2 is ‘Evading Growth Suppressors’. Earlier I said that normal cells know when to grow and divide and when to stop and this is how our body grows, repairs and maintains itself in this post. We already talked about how cells must get a signal to grow. Once that signal is received, the cell will enter the Cell Cycle, which is an orderly process to grow and divide cells. In the cell cycle, the cell must grow in size (G1 phase), double its DNA (S phase), grow a little more (G2 phase) and divvy that DNA equally and divide into two cells (M phase). To keep things in order, there are checkpoints built in where the cell pauses and assesses the situation to make sure all is clear to proceed. If the original DNA is damaged, it should be noticed at the G1/S checkpoint (blue star) and the brakes should be applied. If the cell makes it past that checkpoint and the DNA is doubled but an error had occurred in the process, then that should be recognized at the G2/M checkpoint (red star). These brakes are proteins called growth suppressors and they should signal the cell to STOP dividing. So how does cancer get around this?
I like to simplify cellular signaling to a lock and key method. The signal (growth suppressor in this scenario) is the key and the lock is located on the surface of the cell that needs to behave. So let’s say that the cell is dividing happily, but in the process an error is made in DNA replication and it is recognized at the second checkpoint G2/M. A growth suppressor key will be made and it should go and find the lock on that bad cell and shut it down. Unfortunately, cancer cells can stop the production of locks so they aren’t there for the keys to find or there are less of them. This process is called downregulation. Cancer cells can also change the locks so the key doesn’t fit anymore (mutate the site)! Lastly, some cancers directly affect the key production itself by making faulty keys or shutting down the production of keys and then there are really no brakes to the system.
So now if you think back to Hallmark #1, something has erroneously flipped the switch to ON and the cancer cells are all in the cell cycle and dividing away rapidly and in Hallmark #2 the brakes are not being applied, so the cancer cell marches on. We are only on Hallmark 2/10…can you imagine how out of control these cells are going to be by #10? Of note, I had someone ask me today if all cancer cells have all 10 hallmarks….and the answer is generally yes with some exceptions.
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