Figure S1
20
Figure S1 A. B. * * * * * * * * * * * * *
description
Figure S1. A. *. *. *. B. *. *. *. *. *. *. *. *. *. *. Figure S2. A. Fold Increase. OxPhos Genes. B. Figure S3. A. ECAR ( mpH /min) or OCR ( pmol /min). C. SEL-Resistant. SEL-Sensitive. Relative Luciferase Activity (ATP). B. SEL-Sensitive. SEL-Resistant. - PowerPoint PPT Presentation
Transcript of Figure S1
Figure S1
A.
B.
*
**
*
*
* *
**
*
*
**
Figure S2
A.
B.
Fold
Incr
ease
OxPhos Genes
Figure S3
Conc
entr
ation
(mm
ol/L
)
SEL-ResistantSEL-Sensitive
B.
Rela
tive
Luci
fera
se A
ctivi
ty (A
TP)
C.
SEL-ResistantSEL-Sensitive
ECAR
(mpH
/min
) or
OCR
(pm
ol/m
in)
A.
SEL-ResistantSEL-Sensitive
Figure S4
Sensitivity Groups
OC
R (
pmol
es/m
in)
0
50
100
150
200
250
P < 0.0001 CI >1.0
CI <1.0
Figure S5
Dea
d C
ells
(%
)
A. O
CR (p
mol
es/m
in)
B.
PGC1
α [
Trea
tmen
t : M
ock]
C.
Figure S6
D24D24_0.5hD24_3hD24_12hD24_24hD29D29_0.5hD29_3hD29_12hD29_24hWM1799WM1799_0.5hWM1799_3hWM1799_12hWM1799_24hUCSD354LUCSD354L_0.5hUCSD354L_3hUCSD354L_12hUCSD354L_24hSKMEL5SKMEL5_0.5hSKMEL5_3hSKMEL5_12hSKMEL5_24hMEL624MEL624_0.5hMEL624_3hMEL624_12hMEL624_24h
JN
K_
pT
183-T
185
C-R
af_
pS
338
HE
R2
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et_
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Mre
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Chk2_p
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ha-C
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nin
beta
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cl-2
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B.
P-S6 (S235_S236)
Rela
tive
Prot
ein
Leve
ls
D24 D29 WM1799 UCSD354 SKMEL5 MEL624
P-AKT (T308)
Rela
tive
Prot
ein
Leve
ls
D24 D29 WM1799 UCSD354 SKMEL5 MEL624
Cl. Caspase 7
Rela
tive
Prot
ein
Leve
ls
D24 D29 WM1799 UCSD354 SKMEL5 MEL624
Figure S6
P-MAPK (T202_Y204)
Rela
tive
Prot
ein
Leve
ls
D24 D29 WM1799 UCSD354 SKMEL5 MEL624
C.
Figure S6
D.
MAPK & mTOR1/2 Activity Proliferation Apoptosis Tumor Suppression RTK Activation AKT Activity
WM3854_ConWM3854_AZD6244WM3854_AZD8055WM3854_6244+8055WM1361_ConWM1361_AZD6244WM1361_AZD8055WM1361_6244+8055
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af
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ad
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Fib
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0 500 1000 1500MITF
0.0
0.5
1.0
1.5
2.0
Combination Index
MutationBRAF
NRAS
WT
R2=0.32p=0.03
0 500 1000 1500MITF
50
100
150
200
OCR
MutationBRAF
NRAS
WT
R2=0.54p=0.002
Figure S7
A. B.
Figure S7
E.
RLU
WM3854
mRN
A [T
reat
men
t : M
ock]
MEL624C.
mRN
A [T
reat
men
t : M
ock]
WM3854D.
Figure S8
DAPI
MITF
Merge
Mock SEL AZD8055 SEL+8055
A.
Figure S8
RLU
MEL624B.
** *
RLU
MEL624C.
* * *
Figure S8
D.
MEL624
Risc
PGC1
a
MIT
F
mTO
R
RAPT
OR
RICT
OR
RAPO
R+RI
CTO
R
PGC1α
MITF
mTOR
P-AKT(S473)
P-4EBP1(S65)
P-S6(S235/236)
Raptor
Rictor
S6
AKT
WM3854Ri
sc
PGC1
a
MIT
F
mTO
R
RAPT
OR
RICT
OR
RAPT
OR+
RICT
OR
PGC1α
MITF
mTOR
P-AKT(S473)
P-4EBP1(S65)
P-S6(S235/236)
Raptor
Rictor
S6
AKT
Rela
tive
Inte
nsity
Figure S9
A.
Mock
B.
2014
8055
Effect of mTORC1/2 Inhibition
C.
Mo
ck
SE
L
AZ
D80
55
SE
L+
AZ
D80
55
PGC1α
MITF
GAPDH
AZ
D20
14
SE
L+
AZ
D20
14
Figure S10
% In
hib
itio
n
SEL (mM)
A.
% In
hib
itio
n
B.
SEL (mM)
OCR
(pm
ol/m
in/2
5,00
0 ce
lls)
Time (min)
O F C.
P-M
APK
D.
Parental Clone R1 Clone R2
E.
P-S6
Parental Clone R1 Clone R2
Figure S10
Figure S11
A375 A375-R1
Inhi
bitio
n (%
)
A375-R2
Concentration (mM) Concentration (mM) Concentration (mM)
A. B. C.
Inhi
bitio
n (%
)
Concentration (mM) Concentration (mM) Concentration (mM)
D. E. F.WM35 WM35-R1 WM35-R2
Figure S11
G.
A375
A375-R1
Mock Sel AZD8055 Sel+8055
Figure S12
Patient samples
mR
NA
[P
rog
: P
re]
A.
Figure S12
59 Melanomas
166 Lung Cancers
172 Hematopoietic & Lymphoid Cancers
Rela
tive
PGC1
a E
xpre
ssio
n
Cancers by Tissue Type
59 Melanomas
B.
