concise fcs

Question 1

resisting cell death

Answer 1

BCl-2 over-expression
BAK/BAD antagonists
impaired p53 pathway

TRAIL pathway mutations:
FADD mutations
RTK down-regulation
decoy up-regualtion

Question 2

invasion and metestasis

Answer 2

{COLONISATION:}
MMPS, CAFs and TAMs
(MMP-2 and -9)

{ADAPTATION:}
EMT /TWIST /SNAIL and SLUG
INTRAVASATION
heamatopoietic route
transendothelial migration
EXTRAVASATION
PDL-1 checkpoint
Warburg effect

Question 3

How do MMPs degrade the ECM?

Answer 3

break BM components allowing transendothelial migration
MMP-2 and -9 overexpression is observed in melanoma anf colorectal cancer
TGF-B and VEGF

Question 4

inducing angiogenesis

Answer 4

ANGPT1 and Tie2 = triggers Grb2 = MAPK pathway
ANGPT2

VEGF AND THROMBOSPONDIN-1

Question 5

cell cycle deregulaiton

Answer 5

mutations in TP53 - bypass G1/S checkpoint
upstream ATM mutations
hyperactivity of cyclins and CDKs
downreg. of CDK inhibitors

Question 6

MMPs

Answer 6

break collagen and elastin barriers of BM in ECM
-2 and -9 degrade type IV collagen in BM
release VEGF for angiogenesis

Question 7

what do type 3 and 9 MMPs do?

Answer 7

degrade type IV collagen in BM

Question 8

CAFs

Answer 8

produce TGF-β, HGF, FGF (cytokines and GFs)
to trigger EMT
TME modification
promote pro-oncogenic signals

Question 9

TAMs

Answer 9

act with the M2 phenotype
suppress cT cells - immune evasion
migration tracts
secrete VEGF, chemokines, MMPs

Question 10

what cancers see an overexpression of MMP-2 and -9

Answer 10

metastatic melanoma and colorectal cancer.

Question 11

what is EMT (endothelial-to-mesenchymal transition)
triggered by?

Answer 11

triggered by hypoxia, GFs like TGF-β, inflam cytokines like IL-6

Question 12

explain EMT (endothelial-to-mesenchymal transition) and what is upregulated and downregulated to enforce it?

Answer 12

endothelial cells acquire mesenchymal traits
downreg - E-cad = loss of cell-cell junction = DETACHMENT
upreg - N-cad = mesenchymal marker = promoted by TWIST transc. factor = MOTILITY
Release of SNAIL and SLUG = more MMPs = ECM remodelling

Question 13

how does cancer initiate metastasis?

Answer 13

production of GFs to initiate EMT
upreg of transcription factors
angiogenetic link
metabolic shifts - WARBURG effects

Question 14

role of protein kinases in signal transduction and post-translational modification.

Answer 14

Phosphorylation of Target Proteins
Activation of Signalling Cascades
Alter Activity

• Tyrosine Kinases
• Dual-Specificity Kinases - MAPK

SH2 and SH3 regulate kinase activity