figure’s1 a c b · g cv vg 13 c g 13 c egfr up egfr dn myc cell cycle b c v g 13 c 0.00 0.05 0.10...

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FIGURE S1 A C D E B

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Page 1: FIGURE’S1 A C B · G CV VG 13 C G 13 C EGFR UP EGFR DN MYC CELL CYCLE B C V G 13 C 0.00 0.05 0.10 M Axin-2 * * ** ns V G 13 C 0 2 4 6 8 M Myc * * ** V G 13 C 0 20 40 60 80 100 M

FIGURE  S1A C

D E

B

Page 2: FIGURE’S1 A C B · G CV VG 13 C G 13 C EGFR UP EGFR DN MYC CELL CYCLE B C V G 13 C 0.00 0.05 0.10 M Axin-2 * * ** ns V G 13 C 0 2 4 6 8 M Myc * * ** V G 13 C 0 20 40 60 80 100 M

FIGURE  S2

Gefitinib

AZ1366

Combo

V G 13 C

1

V G 13 CV G 13 CV G 13 C V G 13 C V G 13 CEGFR UP EGFR DN MYC

CELL CYCLEB C

V G 13 C0.00

0.05

0.10

FPKM

Axin-2

****

ns

V G 13 C0

2

4

6

8

FPKM

Myc

*

*

**

V G 13 C0

20

40

60

80

100

FPKM

Birc5

* *** *

*

D

V G 13 C0

50

100

150

200

250

FPKM

CCND1

* ** *

**

A

Hierarchial Clustering normalized by geneof z-scored Log2(FPKM+1)

Combo Gefitinib AZ1366 Vehicle

Hierarchial Clustering normalized by geneof z-scored Log2(FPKM+1)

Combo Gefitinib AZ1366 Vehicle

C3 C4 C1 C2 G4 G3 G1 G2 A2 A3 A4 A1 V1 V4 V2 V3

Hierarchial Clustering normalized by geneof z-scored Log2(FPKM+1)

Combo Gefitinib AZ1366 Vehicle

FPKM

FPKM

V G 13 C WNT HALLMARK

p-­‐val

Log2(FPKM)AAxin-­‐2 c-­‐Myc

Survivin Cyclin-­‐D1 Veh Gef 1366 Combo0

50

100

*F

G0G1

G2

S

E

Page 3: FIGURE’S1 A C B · G CV VG 13 C G 13 C EGFR UP EGFR DN MYC CELL CYCLE B C V G 13 C 0.00 0.05 0.10 M Axin-2 * * ** ns V G 13 C 0 2 4 6 8 M Myc * * ** V G 13 C 0 20 40 60 80 100 M

FIGURE  S3A

B

C

scramble 1-1 1-20.0

0.5

1.0

1.5

*** ***

Axin1 KDscramble 1-1 1-2

0.0

0.5

1.0

1.5

** **

Axin1 KD

scramble 1-1 1-20.0

0.5

1.0

1.5

2.0

** **

Axin1 KD

mRN

A  level

(normalized  to  scram

ble)

0 25 50 75 1000

20000

40000

60000

80000

nM gefitinib

# liv

e ce

lls

gefgef + XAV939

0 25 50 75 1000

20000

40000

60000

80000

100000

nM gefitinib

# liv

e ce

lls

D HCC4006

PC9

**

ns

E

0 1 5 20 500

20000

40000

60000

80000

nM alectinib

# liv

e ce

lls

0103090

H3122 nM  AZ1366

Alectinib AZ1366 CI  value

1  nM10  nM 1.0130 0.6590 0.47

510 0.75

30 0.8990 0.43

20

10 1.04

30 0.57

90 0.31

5010 0.5630 0.4290 0.23

Page 4: FIGURE’S1 A C B · G CV VG 13 C G 13 C EGFR UP EGFR DN MYC CELL CYCLE B C V G 13 C 0.00 0.05 0.10 M Axin-2 * * ** ns V G 13 C 0 2 4 6 8 M Myc * * ** V G 13 C 0 20 40 60 80 100 M

FIGURE  S4A B C

0 25 50 75 1000

20000

40000

60000

80000

nM gefitinib

# liv

e ce

lls

gefgef + az1366

0 25 50 75 1000

20000

40000

60000

80000

nM osimertiinib

# liv

e ce

lls

osiosi + az1366

0 25 50 75 1000

20000

40000

60000

80000

100000

nM gefitinib

# liv

e ce

lls

0 25 50 75 1000

20000

40000

60000

80000

nM osimertinib

# liv

e ce

lls

Gefitinib OsimertinibHCC4006

PC9T790M

* **

nsns

0 50 100 150 200 2500

20

40

60

80

100

Days

Perc

ent s

urvi

val

0 50 100 150 2000

20

40

60

80

100

Days

Perc

ent s

urvi

val

H1650HCC4006

Gef + AZ1366

VehicleGefitinibAZ1366

Vehicle Gef 1366 Gef + 1366-5.0×108

0.0

5.0×108

1.0×109

1.5×109

Lum

ines

cens

e (p

/s)

Vehicle Gef 1366 Gef + 1366-5.0×108

0.0

5.0×108

1.0×109

1.5×109

Lum

ines

cens

e (p

/s)

Vehicle Osi 1366 Osi + 13660

2×108

4×108

6×108

8×108

1×109

Lum

ines

cens

e (p

/s)

HCC4006

H1650

PC9T790M

Vehicle Gef 1366 Gef + 1366-1×1010

0

1×1010

2×1010

3×1010

4×1010

Lum

ines

cens

e (p

/s)

Vehicle Gef 1366 Gef + 1366-5.0×109

0.0

5.0×109

1.0×1010

1.5×1010

Lum

ines

cens

e (p

/s)

Vehicle Osi 1366 Osi + 1366

0

1×1010

2×1010

Lum

ines

cens

e (p

/s)

HCC4006

H1650

PC9T790M

D