Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1100 Chapter 20: Cancer
NORMAL CELL
DIVISION
NORMAL
APOPTOSIS
INCREASED
CELL DIVISION
NORMAL
APOPTOSIS
HOMEOSTASIS
TUMOR
Figure 20–13 Both increased cell
division and decreased apoptosis can
contribute to tumorigenesis. In normal
tissues, apoptosis balances cell division
to maintain homeostasis (see Movie 18.1).
During the development of cancer, either
an increase in cell division or an inhibition
of apoptosis can lead to the increased
cell numbers important for tumorigenesis.
The cells fated to undergo apoptosis are
gray in this diagram. Both an increase in
cell division and a decrease in apoptosis
normally contribute to tumor growth.
NORMAL CELL
DIVISION
DECREASED
APOPTOSIS
TUMOR
after a certain number of population doublings (25–50 for human fibroblasts,
for example). This cell-division-counting mechanism is termed replicative
cell senescence, and it generally MBoC6 depends m20.14/20.13 on the progressive shortening of the
telomeres at the ends of chromosomes, a process that eventually changes their
structure (discussed in Chapter 17). As discussed in Chapter 5, the replication of
telomere DNA during S phase depends on the enzyme telomerase, which maintains
a special telomeric DNA sequence that promotes the formation of protein
cap structures to protect chromosome ends. Because many proliferating human
cells (stem cells being an exception) are deficient in telomerase, their telomeres
shorten with every division, and their protective caps deteriorate, creating a DNA
damage signal. Eventually, the altered chromosome ends can trigger a permanent
cell-cycle arrest, causing a normal cell to die.
Human cancer cells avoid replicative cell senescence in one of two ways. They
can maintain the activity of telomerase as they proliferate, so that their telomeres
do not shorten or become uncapped, or they can evolve an alternate mechanism
based on homologous recombination (called ALT) for elongating their chromosome
ends. Regardless of the strategy used, the result is that the cancer cells continue
to proliferate under conditions when normal cells would stop.
The Tumor Microenvironment Influences Cancer Development
While the cancer cells in a tumor are the bearers of dangerous mutations and
are often grossly abnormal, the other cells in the tumor—especially those of the
supporting connective tissue, or stroma—are far from passive bystanders. The
2 mm
Figure 20–14 Cross-section of a colon
adenocarcinoma that has metastasized
to the lung. This tissue slice shows
well-differentiated colorectal cancer cells
forming cohesive glands in the lung.
The metastasis has central pink areas of
necrosis where dying cancer cells have
outgrown their blood supply. Such anoxic
regions are common in the interior of large
tumors. (Courtesy of Andrew J. Connolly.)