Okay. So now let's talk about the causes of cancer. Cancer mutations can occur in many different ways. One that you may not even be familiar with is that viruses can cause cancer. A significant one that hopefully you're familiar with, because this vaccine came out during your lifetime, is HPV. HPV carries two genes called E6 and E7, and these very easily lead to cancer. They don't do it every time, but they can. Viruses can introduce different genes that can activate cancer-causing genes or interfere with the normal cell pathway that leads to cancer very easily. And so, I'm only mentioning HPV here, but there are lots of others, especially in liver cancer, HCV, hepatitis C, is another example. There's Kaposi's sarcoma, which is found in HIV and AIDS patients, but essentially, these different viruses can lead to cancer. But the good part about viruses leading to cancer is that you can have vaccines against viruses, and therefore, there is a vaccine against HPV. It's the only vaccine that currently exists that is a vaccine against cancer, and so it's super amazing. It's an incredible vaccine, and so, this will actually not only prevent you from getting HPV but can prevent overwhelmingly cervical cancer in women, but also head, neck, and throat cancer in men, which a lot of people don't know about. But viruses can very easily and often cause cancer.

Then a second way is epigenetic changes. Epigenetic changes are changes to the histone protein modifications that are found in the packaging of DNA, and we know that different modifications can cause genes to be overexpressed or genes to be underexpressed. Either way, this is resulting in gene misregulation, causing it not to be expressed correctly. And if a gene is overactivated or underactivated, it can affect regulatory genes that are controlling cell growth, division, and death, and that very easily can lead to cancer.

Viruses, epigenetic changes, and then finally, environmental substances. These are things like cigarette smoke, which we definitely know cause cancer. It can also be exposure to UV rays in the sun or tanning beds. It can be exposure to certain chemicals, like asbestos, but essentially all these different environmental substances that we encounter all the time, can very easily lead to a mutation or multiple mutations that can accumulate over time if you're exposed to various different ones, and those accumulation of mutations will lead to cancer because they'll affect cell growth, division, and death.

So those are some of the causes of cancer. Now, one way that these causes all sort of come together and really cause cancer is through misregulation of the cell cycle. Misregulation of the cell cycle is one way these mutations can affect a single cell. And so, essentially, misregulation of the cell cycle is obviously going to affect everything from growth, division, and death, which are the 3 main facets of cancer. And so how the cell cycle is regulated is actually through different proteins. Some of these proteins are called cyclins, and some of these proteins are called cyclin-dependent kinases. A kinase is going to add phosphate, and when phosphates are added to proteins, that can activate more proteins. The cell cycle has these different regions called checkpoints, and at different checkpoints, these proteins called cyclins, and the proteins that depend on cyclins, the cyclin-dependent kinases, have to be appropriately regulated at these different points to allow a cell cycle to continue. An example of some of these cell cycle checkpoints includes G1 to S. So remember the phases of the cell cycle is G1, then you have S, then you have G2, then you have M, and then you back to the interface. This is the cell cycle here. The G1 to S transition, in S, DNA replication occurs, and the cell does not want to replicate damaged DNA, so it stops here and it checks to make sure that the DNA is right. It's not damaged, and if it is damaged, it repairs it. An important protein that you'll read about that is important in this transition is retinoblastoma, and we'll talk about this protein a little bit more in later videos, but essentially, this is a transcription factor. And what do transcription factors do? They regulate gene expression. The retinoblastoma transcription factor is really important in the G1 to S transition, making sure that the DNA is appropriately repaired and is correct before replicating it. The second one is G2 to M, and this is making sure DNA replication has gone correctly. DNA was replicated here, and now the cell wants to stop before it divides and make sure something hasn't gone incredibly wrong with DNA replication, which makes sense. Right? If your DNA is replicated wrong, then that can induce a lot of different mutations that can very easily lead to cancer. Here's a cyclin called CDC2, and Cyclin B, and this is the cyclin, and these are important in these transitions. You don't necessarily need to know these, that's for cell biology for most of you, but, just know that cyclins and these cyclin-dependent kinases are here. So if we look at this sort of graph, the different phases, G1 phase, DNA replication happens here in the S phase, G2 phase, and mitosis. You can see that different cyclins activate at different times where cyclin E is going to really affect the G1 to S transition, where, you know, cyclin B, for instance, will really affect this G2 to M transition. And there are these different concentrations of cyclins that happen over time, and the different concentrations of cyclin affect the cyclin-dependent kinases that go on to add phosphates to different proteins in the G2 phase, and it's like, oh, wait, we need to do something else, let's start over. And it will, it will actually go back, it will start over, it will pause and make sure that everything is right before mitosis continues. Now, you can imagine if mutations happen in these regions, in these proteins that are regulating these sections, or any of the proteins that are going to have phosphate added to them by the kinases, then this whole system will get messed up and that is what allows mutations to accumulate over time to pass through mitosis because it says, oh, I have a mutation, but don't worry about it. We can move on. We don't need to check it and repair it. Oh, the DNA wasn't replicated correctly. Oh, don't worry about it. We'll move on. We don't have to correct it. Impacting these pathways is super important in creating this abnormal growth, proliferation, and death and preventing it from happening in normal cells, and that leads very easily to cancer. So, I know that's a mouthful, but with that as the overview of cancer, let's now move on.