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 them^1
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Diagram showing different responses of normal and cancer cells to growth factor presence or absence.
- Normal cells in a culture dish will not divide without the addition of growth factors.
- Cancer cells in a culture dish will divide whether growth factors are provided or not.
Diagram showing different responses of normal and cancer cells to growth factor presence or absence.
Normal cells in a culture dish will not divide without the addition of growth factors.
Cancer cells in a culture dish will divide whether growth factors are provided or not.
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 body^2
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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 die^3
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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 division^4
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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 division^5
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Diagram showing different responses of normal and cancer cells to conditions that would typically trigger apoptosis.
- A normal cell with unfixable DNA damaged will undergo apoptosis.
- A cancer cell with unfixable DNA damage will not undergo apoptosis and will instead continue dividing.
Explanation:
