Biomedical Engineering Reference
In-Depth Information
for cancer cells to develop into and maintain malignancy. These include (1) self-sufi ciency in growth
signals, (2) insensitivity to antigrowth signals, (3) evading apoptosis, (4) limitless replicative poten-
tial, (5) sustained angiogenesis, and (6) tissue invasion and metastasis.
23.1.2 A
CQUIRED
C
APABILITIES
OF
C
ANCER
C
ELLS
1. Self-sufi ciency in growth signals can be achieved directly by the production of growth-
promoting signaling molecules by the cancer cell itself. This phenomenon is known as
autocrine stimulation, thus creating a positive growth feed back loop. The production
of platelet derived growth factor (PDGF), transforming growth factor
) by
cancer cells are examples. Another way of achieving self-sufi ciency in growth signals
is to constitutively activate downstream signal transduction pathways normally acti-
vated by progrowth signals. The SOS-Ras-Raf-MAPK signal (Figure 23.1) transduc-
tion pathway is a good example, and the Ras proteins are indeed altered in 25% of all
cancers leading them to produce mitogenic signals in the absence of progrowth signals
(Figure 23.1).
α
(TGF-
α
Receptor
e.g., HER2
VEGF
Plasma membrane
P
P
Cytoplasm
SOS
PI3-K
Ras
Raf
AKT
MEK1/2
MAPK
Proliferation
survival
mobility
Nucleus
Transcription
FIGURE 23.1
Cartoon depicting two signal transduction cascades often deregulated in cancer, namely, the
PI3K-AKT and the SOS-Ras-Raf-Mek cascades. One way of activating these pathways is by signaling through
the HER2 transmembrane tyrosine kinase receptor.
