Web & Social Media Analytics Previous Year Question Paper.pdf
mol-med-pathways-table copy.pdf
1. Pathway Oncogenes/Oncoproteins Tumor Suppressors Pathology
MAPK
pathway
-Proliferative
Growth Factors: PDGF,
VEGF and HGF
RTK: HER2/NEU &
EGFR/ERBB1 -
constitutively active
G protein: RAS - mutation
that decreases activity of
GTPase, GTP bound
longer & signalling
continues.
Kinase: RAF constitutively
active
Transcription factors:
FOS mutated or
overexpressed
Phosphatases to
switch off the pathway
thus the phosphatases
are tumour
suppressors.
There are proteins
called GAPS (GTPase
activating proteins)
which activate G
protein GTPase
activity. If their
function is lost or
decreased, G proteins
are active longer, thus
GAPS are also tumour
suppressors
Growth Factors: form an
autocrine loop that activate
tumor cells (sarcomas)
RTK:
HER2/NEU & EGFR/ERBB1 –
lung & breast carcinoma
EGFR/ERBB1 - lung, breast
carcinomas & gastro-
intestinal stromal tumours
G protein: many cancers
Kinase: melanomas
PI3K pathway
-Pro-survival,
growth,glucose
uptake
Same growth factors &
receptors as for MAPK
pathway
PI3K gene - hyperactive
enzyme & is amplified
resulting in
overexpressed enzyme.
AKT gene – constitutively
active & is amplified
resulting in
overexpressed protein
PTEN removes
phosphate from PIP3
converting it to PIP2,
therefore there is no
docking site for the PH
domain of AKT & AKT
is not activated
PI3K pathway switched
off
Therefore, if PTEN lost
→ Continuous
signalling through PI3K
pathway
PI3K gene: ovarian carcinoma,
hepatocellular carcinoma,
breast carcinoma
PTEN gene: a common target
for mutation in sporadic
cancers.
Germline mutations in the
PTEN gene have been
implicated
in the development of
Cowden’s disease where
there is an increased risk of
breast and thyroid cancers.
2. JAK-STAT
pathway
JAK: constitutively active
without needing cytokine
to bind to receptor
STAT: constitutively
active
SOCS (Suppressors of
Cytokine Signalling) -
Inhibits JAK
JAK mutations are particularly
important in
myeloproliferative
disorders:
Polycythaemia vera –
increased RBCs (up to 99% of
cases)
Essential thrombocytosis –
increased platelets (up to 72%
of cases)
Pathway Oncogenes/Oncoproteins Tumor Suppressors Pathology
WNT
pathway
WNT - is overexpressed
or inappropriately
expressed
β Catenin - the gene is
mutated so that the
protein is not recognised
by ubiquitin E3 ligase and
not degraded or
- The gene is amplified so
that there is an
overexpression of β
catenin which
overwhelms the
degradation complex
APC gene product: a scaffold
protein APC that binds to
various proteins, including -
Catenin and AXIN to form
degradation complex,
suppressing WNT signalling
Disregulation of colon
epithelium proliferation
caused by mutations in APC is
implicated in the initiation and
expansion of colon cancer.
APC gene mutations have
been found in most colon
cancers as
well as in other cancers,
such as those of the liver
Colorectal cancer:
APC mutation one of earliest
events
Germline APC mutations:
familial adenomatous
polyposis (FAP)
Sporadic colon cancers (60-
80% APC loss)
Β Catenin also mutated:
activated and results in
increased transcription of
MYC, G1 Cyclin
3. Pathway Oncogenes/proteins Tumor Suppressors Pathology
The
Cell
Cycle
G1 cyclin -
overexpressed or
inappropriately
expressed →
Increased cycling
through the cell
cycle
CDK - constitutively
active or
overexpressed CDK
protein → increased
cell cycling.
RB1 gene: encodes RB which
suppresses growth during the G1
phase of the cell cycle by binding
transcription factor E2F when
hypophosphorylated.
E2F results in increased
expression of genes including the
gene for S cyclins thus ensuring
the progression of the cell cycle.
If RB is lost or mutated so that it
cannot bind E2F, the cell cycle
would continue without needing
the activation of CDK2.
E2F gene has also been found
amplified or mutated in cancers
resulting in overexpressed E2F
protein or one that can’t bind RB
- increased cell cycling.
P53 transcription factor (coded
by TP53): If mutated, cell cycle is
not halted, DNA is not repaired,
apoptosis or senescence is not
initiated and EMT and
angiogenesis is not inhibited.
The RB1 gene is lost in
retinoblastoma and
other tumour types
DNA tumour viruses
produce viral proteins
which bind to RB,
releasing E2F
– Human Herpes Virus
8 (HHV-8, Kaposi's
Sarcoma Herpes
Virus)- LANA-1 protein
– HPV (human
papilloma virus): E7
protein
Many oncogenic DNA
viruses produce viral
proteins that bind to
p53 and inactivate its
function
– Human Herpes Virus
8 (HHV-8, Kaposi's
Sarcoma Herpes
Virus)- LANA-2
– Hepatitis B virus -
HBx – HPV: E6 protein