Why Do Cancer Cells Promote Cancer?

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.

Normal Cell Cycle

The cell cycle describes the various stages through which a dividing cell passes.

After mitosis, a cell goes into G1 (growth 1 phase) during which it increases in size. Most cells

Many of these differences are related to cell division behaviour. e.g. 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 neighbouring cells into producing growth factors to sustain them .

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.

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. 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

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 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.

Overactive (cancer promoting) forms of these genes are called oncogenes,

While the normal, not-yet-mutated forms are called proto-oncogenes.

Normal proto-oncogene can turn into an oncogene if it mutates in a way that increases its activity.

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 protooncogene to part of a different gene, producing a “combo” protein with unregulated