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How cancer cells evade apoptosis:1. Decoy Receptor Expression: Cancer cells can escape apoptotic programming by upregulating the expression of non-signaling decoy receptors for the FAS ligand which may prevent activation of the FAS receptor and downstream apoptosis. 2. Elevated Oncogene Signaling: Persistent and/or elevated signaling from oncogenes can drive cell proliferation that can shift the balance over a cell’s apoptotic program. 3. Upregulated Apoptosis Inhibiting Pathways: Cancer cells can overcome apoptosis via the upregulation of apoptosis inhibiting pathways, such as the PI 3 kinase (PI 3K)-Akt/PKB survival pathway and BCL2 overexpression. Loss of the tumor suppressor gene PTEN also inhibits apoptosis. 4. p53 Mutations: The pro-apoptotic regulator, p53, is a key tumor suppressor and is mutated in many cancers.
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1. Decoy Receptor ExpressionCancer cells can escape apoptotic programming by upregulating the expression of non-signaling decoy receptors for the FAS ligand which may prevent activation of the FAS receptor and downstream apoptosis.
2. Elevated Oncogene SignalingPersistent and/or elevated signaling from oncogenes can drive cell proliferation that can shift the balance over a cell’s apoptotic program.
3. Upregulated Apoptosis Inhibiting PathwaysCancer cells can overcome apoptosis via the upregulation of apoptosis inhibiting pathways, such as the PI 3 kinase (PI 3K)-Akt/PKB survival pathway and BCL2 overexpression. Loss of the tumor suppressor gene PTEN also inhibits apoptosis.
4. p53 MutationsThe pro-apoptotic regulator, p53, is a key tumor suppressor and is mutated in many cancers.
How cancer cells evade apoptosis:
www.millipore.com/cancer
TNFα
FasL
Fas
TNFR1
GrowthFactor
Growth FactorReceptor
Withdrawal ofGrowth Factors
Depolarization
OncogenicSignal
Apo2/Apo3
Apo2L/Apo3L
APOPTOSIS EVASION IN CANCER CELLS
ELEVATED ONCOGENE SIGNALING2
DECOY RECEPTOR EXPRESSION1
p53 MUTATIONS4
MDM2
UPREGULATED APOPTOSIS INHIBITING PATHWAYS
3
p53
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Millipore is a registered trademark of Millipore Corporation. The M mark is a trademark of Millipore Cororation. Calbiochem is a registered trademark of EMD Chemicals Inc. Lit. No. PS4623EN00 Printed in U.S.A. 12/10 LS SBU-10-03912 © 2010 Millipore Corporation, Billerica, MA 01821 U.S.A. All rights reserved.
FADD
FADD FADD TRADD
TRAF2
Mitochondria
RIP
PKC
BID
Iκbs
IKKsFLIP
CIAP1
NF-κB
NF-κB
BAD
PBRVDAC
CypD
BAKBAX
IBID
BCLXL
MMP
ANT BIM
PUMANoxa
AIFEndoGApoptosis
Apoptosis
Apoptosis
DNAFragmentation
BAX, BAK, BID,Ras, Noxa, PUMA,APAF1, Survivin
FLIP, CIAP2, BFL1, BCL2
POD
Apoptosis
DNA Fragmentation
p53AIP1
BCL2
p90RSK
RAS
PIP3
PTEN
Procaspase8
Caspase8
Caspase3
Caspase7
ICAD
CAD
Caspase9
APAF1
CytoC
PML PAR4
DaxxZIPK
PARP CAD ATM
Chk2
EndoG
SMAC
Arts
HTRA2
Procaspase8Procaspase8
p53
AIF
p14(ARF)
FasL
Akt1
PI 3-K
GROWTH FACTOR RECEPTOR
PROTEIN KINASES
DEATH-CAUSING PROTEASES
DEATH-INDUCING LIGANDS
GROWTH FACTOR
APOPTOSIS-INDUCING PROTEINS
TRANSCRIPTION FACTORDEATH RECEPTORS
ACTIVATION
INDIRECT ACTIVATION
DOWNSTREAM EFFECT
INHIBITION
TRANSLOCATION
LEGEND
Hallmarksof
Cancer
Self-
suffici
ency
in
prolife
ratio
n sig
nals
Insensitivity to proliferation
inhibiting signals
Evading apoptosis
Tissue invasion &
metastasis
Lim
itle
ss r
eplic
ativ
e po
tent
ial
Sust
ained
angio
gene
sis
Metabolic reprogramming
Escape from
immune controlATP
STOP
