The adult body has roughly 37 trillion cells. If we had to organize all of that, it would be a logistical nightmare. In many ways, it is, but luckily, we don’t have to organize everything from here. We certainly do some things to maintain ourselves at an executive level, like eating when we need sustenance, but a lot of it is up to our cells. Each of our 37 trillion cells puts in enormous amounts of effort to ensure our bodies keep running smoothly, without our brains having to oversee every step of the process. Our cells have a handful of crucial genes that keep our cells healthy. They do things like prevent cell division or cause a cell to self-destruct if the cell is damaged or doesn’t have enough food. Because of their role in protecting the cell, when our DNA is damaged in these specific genes, it can lead to various diseases, including cancer. But these aren’t the only genes that can lead to cancer if they’re damaged.

When our DNA is damaged in certain genes, for one reason or another, the gene can lose its function. But what if our DNA was damaged in a way that activated certain genes? That’s exactly the case with oncogenes. To understand oncogenes, we need a bit more context about how cells divide. Cell division is a really delicate process. If done incorrectly, it can lead to serious damage to a cell or even cell death. If things continue to go wrong, it can end in diseases like cancer. Because of how delicate cell division is, the process is very tightly controlled. On one hand, some genes prevent cell division if conditions aren’t right. Many of these are called “tumour suppressors” because they slow or stop rapid cell division, and as a result, hinder the growth of potential cancers.

So, to actually grow into a multicellular organism, and for various other important processes in our body, we also need genes that promote cell division.

If we lose genes that slow or stop cell division, cells will continue to divide and divide. We can see how that could quickly lead to disease. But that wouldn’t be the case for genes that promote cell division. So, you might be wondering, “If you damage genes that promote cell division, isn’t that a guaranteed way of stopping uncontrolled cell growth?” Unfortunately, it’s not that simple. See, not all DNA damage has the same effect. Often, it ends up with a gene losing its function, but in some cases it can lead to the activation of a gene, which is where oncogenes come in.

In normal cells, these genes are still crucial for proper function, and when behaving normally, they don’t lead to disease. Because of that, the healthy genes are actually called “proto-oncogenes”. The prefix “proto” means “the original” or “earliest form of”. So proto-oncogenes are the genes where oncogenes come from, before they become an issue. If proto-oncogenes are damaged and that mutation causes abnormal activation of said gene, things become problematic.

Luckily, our cells know how important regulating cell division is. When something goes wrong in a cell, like oncogenes promoting cell division they shouldn’t, that’s exactly why we have tumour suppressors. The regulation of the cell cycle is balanced by those that prevent and those that promote cell division. So, if an oncogene is activated by itself, this usually isn’t enough to cause cancer. That’s because tumour suppressors can still prevent cell division despite the constant pressure to divide from oncogenes. In fact, in most cases, to become a full-blown cancer, a cell has to mutate a handful of times. Often, cancers come from a combination of mutations to both tumour suppressors and oncogenes. When this happens, we lose the ability to block cell division while simultaneously promoting it, ultimately leading to uncontrolled cell division and cancer.

Cell division is a critical process. It’s what helps us grow from a single cell into the complex, 37 trillion-cell animals we are today. Luckily, it’s not something we have to organize; our cells control it on their own. But, because it’s such an important process, it’s incredibly intricate and tightly regulated. Tumour suppressors prevent cell division when conditions aren’t right. When a cell is damaged, or there aren’t enough nutrients in the environment, tumour suppressors will stop a cell from spiralling out of control. When they’re damaged and lost, we can lose that regulation, and our cells can divide freely. But we also have genes that promote cell division, and just like tumour suppressors, these genes can be damaged. With oncogenes, however, we don’t worry about a gene losing its function; we have to worry about their overactivation. Unfortunately, some DNA damage can in fact activate oncogenes, and these mutations, when paired with mutations in tumour suppressors, are the main drivers of cancer.

I hope you learned a little something this week, but next week, we’re going to talk about polyploid giant cancer cells. They’re what happens when cell division goes wrong… in a bit of a different way.

See you next week!

If you missed last week’s letter, you can read “Many-a-Melanoma” to learn a little more about why there are different kinds of melanoma, even though they all come from the same type of cell.