Essential Cell Biology 5th edition

Cancer
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2. Cancer cells can survive levels of stress and internal derangement
that would cause normal cells to kill themselves by apoptosis. This
avoidance of cell suicide is often the result of mutations in genes that
regulate the intracellular death program responsible for apoptosis
(discussed in Chapter 18). For example, about 50% of all human
cancers have an inactivating mutation in the p53 gene. The p53
protein normally acts as part of a DNA damage response that causes
cells with DNA damage to either cease dividing (see Figure 18−15) or
die by apoptosis. Chromosome breakage, for example, if not repaired,
will generally cause a cell to commit suicide; but if the cell is defective
in p53, it may survive and divide, creating highly abnormal daughter
cells that have the potential for further mischief (Movie 20.8).
3. Unlike most normal human cells, cancer cells can often proliferate
indefinitely. Most normal human somatic cells will only divide a
limited number of times in culture, after which they permanently
stop; this cessation of proliferation—called cell senescence—occurs,
at least in part, because many cells in the adult organism lose the
ability to produce the enzyme telomerase. The telomeres at the ends of
their chromosomes thus become progressively shorter with each cell
division (see Figure 6−22). In cultured cells, this erosion of telomerase
sequences can activate a DNA damage response that permanently
halts cell proliferation. Cancer cells typically break through this
proliferation barrier by reactivating production of telomerase, enabling
them to maintain telomere length indefinitely.
4. Most cancer cells are genetically unstable, with a greatly increased
mutation rate and an abnormal number of chromosomes (see Table
20–1 and Figure 20–44).
5. Cancer cells are abnormally invasive, at least partly because they
often lack certain cell adhesion molecules, such as cadherins, that
help hold normal cells in their proper place.
6. Cancer cells are abnormally avid for nutrients, which they use to
generate much of their ATP by glycolysis in the cell cytosol. This process
is less efficient than producing ATP by oxidative phosphorylation in
the mitochondria, but is useful for fast-growing tumors in which cells
in the interior are often oxygen-deprived.
7. Cancer cells can survive and proliferate in abnormal locations,
whereas most normal cells die when misplaced. This colonization
of unfamiliar territory may result from the ability of cancer cells to
produce their own extracellular survival signals and to suppress their
apoptosis program (as described in #2, above).
8. As cancer cells evolve, they secrete signals that influence the behavior
of cells in the surrounding connective tissue, thereby modifying the
tumor’s microenvironment. Cells in the remodeled microenvironment,
in return, produce signals that support the survival and proliferation
of the cancer cells, which renders the microenvironment even more
hospitable for tumor growth.
To understand these abnormal properties of cancer cells, we have to
identify the mutations responsible.
Two Main Classes of Genes Are Critical for Cancer:
Oncogenes and Tumor Suppressor Genes
Investigators have made use of a variety of approaches to track down the
genes and mutations that are critical for cancer—from studying viruses
that cause cancer in chickens to following families in which a particular
cancer occurs unusually often. Though many of the most important of
these genes have now been identified, the hunt for others continues.
For many of the cancer-critical genes, the most dangerous mutations are
ones that render the encoded protein hyperactive. These gain-of-function
QUESTION 20–8
About 10 16 cell divisions take place
in a human body during a lifetime,
yet an adult human body consists
of only about 10 13 cells. How can
you reconcile these apparently
conflicting two numbers?