If you're seeing this message, it means we're having trouble loading external resources on our website.

If you're behind a web filter, please make sure that the domains *.kastatic.org and *.kasandbox.org are unblocked.

Main content

Cancer and the cell cycle

How cancer can be linked to overactive positive cell cycle regulators (oncogenes) or inactive negative regulators (tumor suppressors). 

Introduction

Does cell cycle control matter? If you ask an oncologist – a doctor who treats cancer patients – she or he will likely answer with a resounding yes.
Cancer is basically a disease of uncontrolled cell division. Its development and progression are usually linked to a series of changes in the activity of cell cycle regulators. For example, inhibitors of the cell cycle keep cells from dividing when conditions aren’t right, so too little activity of these inhibitors can promote cancer. Similarly, positive regulators of cell division can lead to cancer if they are too active. In most cases, these changes in activity are due to mutations in the genes that encode cell cycle regulator proteins.
Here, we’ll look in more detail at what's wrong with cancer cells. We'll also see how abnormal forms of cell cycle regulators can contribute to cancer.

What’s wrong with cancer cells?

Cancer cells behave differently than normal cells in the body. Many of these differences are related to cell division behavior.
For example, cancer cells can multiply in culture (outside of the body in a dish) without any growth factors, or growth-stimulating protein signals, being added. This is different from normal cells, which need growth factors to grow in culture.
Cancer cells may make their own growth factors, have growth factor pathways that are stuck in the "on" position, or, in the context of the body, even trick neighboring cells into producing growth factors to sustain them1.
Cancer cells also ignore signals that should cause them to stop dividing. For instance, when normal cells grown in a dish are crowded by neighbors on all sides, they will no longer divide. Cancer cells, in contrast, keep dividing and pile on top of each other in lumpy layers.
The environment in a dish is different from the environment in the human body, but scientists think that the loss of contact inhibition in plate-grown cancer cells reflects the loss of a mechanism that normally maintains tissue balance in the body2.
Another hallmark of cancer cells is their "replicative immortality," a fancy term for the fact that they can divide many more times than a normal cell of the body. In general, human cells can go through only about 40-60 rounds of division before they lose the capacity to divide, "grow old," and eventually die3.
Cancer cells can divide many more times than this, largely because they express an enzyme called telomerase, which reverses the wearing down of chromosome ends that normally happens during each cell division4.
Cancer cells are also different from normal cells in other ways that aren’t directly cell cycle-related. These differences help them grow, divide, and form tumors. For instance, cancer cells gain the ability to migrate to other parts of the body, a process called metastasis, and to promote growth of new blood vessels, a process called angiogenesis (which gives tumor cells a source of oxygen and nutrients). Cancer cells also fail to undergo programmed cell death, or apoptosis, under conditions when normal cells would (e.g., due to DNA damage). In addition, emerging research shows that cancer cells may undergo metabolic changes that support increased cell growth and division5.

How cancer develops

Cells have many different mechanisms to restrict cell division, repair DNA damage, and prevent the development of cancer. Because of this, it’s thought that cancer develops in a multi-step process, in which multiple mechanisms must fail before a critical mass is reached and cells become cancerous. Specifically, most cancers arise as cells acquire a series of mutations (changes in DNA) that make them divide more quickly, escape internal and external controls on division, and avoid programmed cell death6.
How might this process work? In a hypothetical example, a cell might first lose activity of a cell cycle inhibitor, an event that would make the cell’s descendants divide a little more rapidly. It’s unlikely that they would be cancerous, but they might form a benign tumor, a mass of cells that divide too much but don’t have the potential to invade other tissues (metastasize)7.
Over time, a mutation might take place in one of the descendant cells, causing increased activity of a positive cell cycle regulator. The mutation might not cause cancer by itself either, but the offspring of this cell would divide even faster, creating a larger pool of cells in which a third mutation could take place. Eventually, one cell might gain enough mutations to take on the characteristics of a cancer cell and give rise to a malignant tumor, a group of cells that divide excessively and can invade other tissues7.
As a tumor progresses, its cells typically acquire more and more mutations. Advanced-stage cancers may have major changes in their genomes, including large-scale mutations such as the loss or duplication of entire chromosomes. How do these changes arise? At least in some cases, they seem to be due to inactivating mutations in the very genes that keep the genome stable (that is, genes that prevent mutations from occurring or being passed on)8.
These genes encode proteins that sense and repair DNA damage, intercept DNA-binding chemicals, maintain the telomere caps on the ends of chromosomes, and play other key maintenance roles9. If one of these genes is mutated and nonfunctional, other mutations can accumulate rapidly. So, if a cell has a nonfunctional genome stability factor, its descendants may reach the critical mass of mutations needed for cancer much faster than normal cells.

Cell cycle regulators and cancer

Different types of cancer involve different types of mutations, and, each individual tumor has a unique set of genetic alterations. In general, however, mutations of two types of cell cycle regulators may promote the development of cancer: positive regulators may be overactivated (become oncogenic), while negative regulators, also called tumor suppressors, may be inactivated.

Oncogenes

Positive cell cycle regulators may be overactive in cancer. For instance, a growth factor receptor may send signals even when growth factors are not there, or a cyclin may be expressed at abnormally high levels. The overactive (cancer-promoting) forms of these genes are called oncogenes, while the normal, not-yet-mutated forms are called proto-oncogenes. This naming system reflects that a normal proto-oncogene can turn into an oncogene if it mutates in a way that increases its activity.
Mutations that turn proto-oncogenes into oncogenes can take different forms. Some change the amino acid sequence of the protein, altering its shape and trapping it in an “always on” state. Others involve amplification, in which a cell gains extra copies of a gene and thus starts making too much protein. In still other cases, an error in DNA repair may attach a proto-oncogene to part of a different gene, producing a “combo” protein with unregulated activity10.
Many of the proteins that transmit growth factor signals are encoded by proto-oncogenes. Normally, these proteins drive cell cycle progression only when growth factors are available. If one of the proteins becomes overactive due to mutation, however, it may transmit signals even when no growth factor is around. In the diagram above, the growth factor receptor, the Ras protein, and the signaling enzyme Raf are all encoded by proto-oncogenes11.
Overactive forms of these proteins are often found in cancer cells. For instance, oncogenic Ras mutations are found in about 90% of pancreatic cancers. Ras is a G protein, meaning that it switches back and forth between an inactive form (bound to the small molecule GDP) and an active form (bound to the similar molecule GTP). Cancer-causing mutations often change Ras’s structure so that it can no longer switch to its inactive form, or can do so only very slowly, leaving the protein stuck in the “on” state (see cartoon above)12.

Tumor suppressors

Negative regulators of the cell cycle may be less active (or even nonfunctional) in cancer cells. For instance, a protein that halts cell cycle progression in response to DNA damage may no longer sense damage or trigger a response. Genes that normally block cell cycle progression are known as tumor suppressors. Tumor suppressors prevent the formation of cancerous tumors when they are working correctly, and tumors may form when they mutate so they no longer work.
One of the most important tumor suppressors is tumor protein p53, which plays a key role in the cellular response to DNA damage. p53 acts primarily at the G1 checkpoint (controlling the G1 to S transition), where it blocks cell cycle progression in response to damaged DNA and other unfavorable conditions13.
When a cell’s DNA is damaged, a sensor protein activates p53, which halts the cell cycle at the G1 checkpoint by triggering production of a cell-cycle inhibitor. This pause buys time for DNA repair, which also depends on p53, whose second job is to activate DNA repair enzymes. If the damage is fixed, p53 will release the cell, allowing it to continue through the cell cycle. If the damage is not fixable, p53 will play its third and final role: triggering apoptosis (programmed cell death) so that damaged DNA is not passed on.
In cancer cells, p53 is often missing, nonfunctional, or less active than normal. For example, many cancerous tumors have a mutant form of p53 that can no longer bind DNA. Since p53 acts by binding to target genes and activating their transcription, the non-binding mutant protein is unable to do its job14.
When p53 is defective, a cell with damaged DNA may proceed with cell division. The daughter cells of such a division are likely to inherit mutations due to the unrepaired DNA of the mother cell. Over generations, cells with faulty p53 tend to accumulate mutations, some of which may turn proto-oncogenes to oncogenes or inactivate other tumor suppressors.
p53 is the gene most commonly mutated in human cancers, and cancer cells without p53 mutations likely inactivate p53 through other mechanisms (e.g., increased activity of the proteins that cause p53 to be recycled)14,15.

Check your understanding: viruses and cancer

Some forms of cancer are linked to specific types of viruses. For instance, infection with certain strains of human papillomavirus can lead to cervical cancer. This virus encodes a protein called E6, which binds to the p53 protein. Which of the following explains why papillomavirus can cause cancer?
Choose 1 answer:

Want to join the conversation?

  • duskpin sapling style avatar for user Ahmed
    How does DNA get damaged in the first place?
    (18 votes)
    Default Khan Academy avatar avatar for user
  • starky ultimate style avatar for user alina
    Could you make a cancer-like cell, or rather a cell that has a mutation that makes it and its offspring grow into a neoplasm, and have their mutation be GOOD? The article says that cancer cells are known to be immortal, so if that's the case, could you use "good" neoplasms to fight cancerous ones that would later form tumors? Thanks to anyone who can understand my question :-)
    (15 votes)
    Default Khan Academy avatar avatar for user
    • leafers ultimate style avatar for user William H
      It is feasible, however the main issue is you don't want to introduce some foreign type of human mutated and immortal cancer without the full ability to knock it out and rein it in. Probably there will be treatments that revolve around this whether is be putting drug producing genes in cells that surround a cancer, although it wouldn't exactly be wise to use a cancer cell to fight a cancer cell by definition, since there are better cell options out there. However if such a cell was discovered tomorrow that didn't grow very fast, only grew near tumors, somehow produced weapons to fight it, no doubt it would become a very popular therapy, however a non-cancerous cell may do the trick better without the risk of it turning into actual cancer.
      (17 votes)
  • duskpin ultimate style avatar for user RacheLee
    It might not be directly related to this topic, but I have a question. Can cancer be inherited? or does it just depends on your normal habits?
    (8 votes)
    Default Khan Academy avatar avatar for user
    • piceratops sapling style avatar for user haekele
      Some people are born with a gene mutation that they inherited from their mother or father. This damaged gene puts them at higher risk for cancer than most people. When cancer occurs because of an inherited gene mutation, it is referred to as "hereditary cancer."
      Although this is often referred to as inherited cancer, what is inherited is the abnormal gene that can lead to cancer, not the cancer itself.
      (14 votes)
  • blobby green style avatar for user John Morgenthaler
    Why not engineer a retrovirus to insert an extra copy of the P53 gene? First as a treatment for people with a dangerous cancer, then try it on people who have only one working copy of P53?
    (13 votes)
    Default Khan Academy avatar avatar for user
    • blobby green style avatar for user 6002t1023
      I think there are several reasons why this isn't a treatment (yet). I'm sure there's a lot you have to figure out before you can get a virus to successfully insert a copy of the gene. There may be some epigenetic factors that would make this technique not work very well and nobody has figured out how to get around that yet.
      (4 votes)
  • female robot grace style avatar for user Bezawit
    So, I was wondering what could happen if P53 is introduced to cancer cells, once they have mutated. May be, introducing a functional P53 to cancer cells before they progress so far, could prevent them. Is it possible ? What do you say? Please answer
    (6 votes)
    Default Khan Academy avatar avatar for user
    • aqualine ultimate style avatar for user Lau Sky
      I was thinking the same thing! except maybe giving immunization shots to fix the DNA in earlier stages like when you are just born. But it would definitely be interesting to see if it worked after the patient had cancer. I think it could possibly work afterwards, but the only problem is, if the cancer is already affected large parts of the body, and the P53 activates the apoptosis, then you could kill of a large amount of cells in your body, too much to live. Other than that, I think this would completely work.
      (3 votes)
  • piceratops ultimate style avatar for user paul
    Besides chemo and radiation, what other cures are there for cancer?
    (5 votes)
    Default Khan Academy avatar avatar for user
  • spunky sam green style avatar for user jgingold533
    Can cancer become so cancerous that kills itself? Could so many mutations accumulate that it would not be able to divide anymore?
    (5 votes)
    Default Khan Academy avatar avatar for user
    • winston baby style avatar for user Ivana - Science trainee
      Interesting question!

      Definitely, yes. But do not rely on that. Once there are too many mutations accumulated it is too late and it will affect healthy cells as well. You mean, mutations which trigger apoptosis, right? In that case, cancer would resemble an auto-immune disease.


      Other than that it is not possible for cancer to just 'kill itself', moreover it thrives really well and always finds a way to grow and spread.
      (4 votes)
  • orange juice squid orange style avatar for user Artem Anisimov
    So, how long does cancer cell cycle take compared to normal cell?
    (4 votes)
    Default Khan Academy avatar avatar for user
    • purple pi purple style avatar for user Jay
      That depends if it is a benign tumor (not to bad) or a bad tumor (I cannot spell its name). If the tumor is benign the cells it contains will split only slightly faster than a normal cell. If it is a dangerous cancerous tumor, then the cells in it will split much faster and more uncontrollably than a normal cell would.

      If a normal cell takes a second to divide and then waits a week and divides again (this is just an example, this is not accurate information) a bad cancer cell might take a second to divide and then wait an hour. If this is the case you will have two good cells from one good cell and 168 bad ones from the cancerous cell. NOTE: this is just an example I made up, real cells divide much quicker and can wait much shorter or longer amounts of time before dividing again, some cells never even divide again.
      (5 votes)
  • purple pi purple style avatar for user Sonakshi
    Is it possible to completely reverse the damage done by cancer cells to the host's DNA? Few form of cancers, which occur due to mutation in DNA, leading to uncontrollable growth of cells, may be treatable by gene therapy by targeting the mutated gene.
    (3 votes)
    Default Khan Academy avatar avatar for user
    • winston baby style avatar for user Ivana - Science trainee
      That sounds like a nice idea but in reality, many mutations cause cancer. Plus there is that variability among cancer cells. What do I mean by that?


      I mean that even within cancerous tissue not all of them are clones. there are genetic variants among them.

      If you prepare gene therapy, how do you know which one to traget? Let's suppose you know which one, - cell variant A. Then you are left off B, C, D.
      If there is left the only one of let's say D, that's enough to regrow and reoccur - several years later. Without you even knowing you left that one cell.
      (6 votes)
  • blobby green style avatar for user princessyoheved
    "In general, human cells can go through only about 40-60 rounds of division before they lose the capacity to divide, "grow old," and eventually die" what factor defines which cell is the old one, and which on is this the new one when the cell divides? if one cell was not younger compared to the original cells, wouldn't all the cells just die at the same time?
    (4 votes)
    Default Khan Academy avatar avatar for user
    • female robot ada style avatar for user Mahima435
      There are A Caps (long strings of adenosine nucleotides) at the end of chromosomes, and as the cell keeps replicating, it starts to wear off. These are what the checkpoints in previous articles talk about. If there is not enough A cap to safely replicate the DNA without it wearing off, then the more important DNA could be damaged irrevocably and could be damaged and the cell would permanently go into G0 stage or apoptosis.
      (3 votes)