Figure 1

Figure 2

a b

MCF10

a

UACC

ZR75.1

MCF7

MB23

1

SKBR30

20

40

60

HX

R9

IC50

(u

M)

p=

0.0

00

9

p=

0.0

01

4

TP53

Unt

CXR9

HXR90.000

0.005

0.010

0.015

0.020

Rel

ativ

e ex

pre

ssio

n

cFos

Unt

CXR9

HXR90.00

0.05

0.10

0.15

0.20

0.25

Rel

ativ

e ex

pre

ssio

n

***

Figure 3

Unt

CXR9

HXR90.00

0.02

0.04

0.06R

elat

ive

exp

ress

ion

a

Unt

CXR9

HXR90.0

0.2

0.4

0.6

0.8

1.0

Rel

ativ

e ex

pre

ssio

n

***b

cFos TP53

Beta actin

cFos TP53

Beta actin

Untreated CXR9 HXR9

Figure 4

b

a

c

**

Untreat

ed

CXR9

HXR9

0

20

40

60

80

100V

N

EA

LA

% c

ells

**

**

**

Figure 5

IC50 (M)Decreasing sensitivity

All HOX genes

SKBR3

MB23

1

MCF7

ZR75.1

UACC

MCF10

aNBT

0

2000

4000

6000M

ean

exp

ress

ion

16 23 33 42 48 51

p=

0.0

02

4

p<

0.0

00

1

p<

0.0

00

1

p<

0.0

00

1

p<

0.0

00

1* * * **

Decreasing sensitivity

HOXB1 to HOXB9

SKBR3

MB23

1

MCF7

ZR75.1

UACC

MCF10

aNBT

0

500

1000

1500

2000

2500

Mea

n e

xpre

ssio

n

16 23 33 42 48 51

p=

0.0

24

3

p=

0.0

00

8

p<

0.0

00

1

p=

0.0

01

2* * *

a b

HOXB1 to HOXB9

20 40 60

-500

0

500

1000

1500

IC50 (uM)

Mea

n e

xpre

ssio

n

r2 = 0.9778p=0.0002

SKBR3

MB231

MCF7

ZR75.1UACC MCF10a

NBT (predicted)

c

HOXB1 to HOXB9

0 20 40 600

2000

4000

6000

8000

10000

IC50 (uM)

Mea

n e

xpre

ssio

n

d

Figure 6

ab

c

0 2 7 9 12 13 19 22 27 30 34 37 40 44 48 500

500

1000

1500

2000CXR9HXR9

Days

Ave

rag

e tu

mo

ur

volu

me

mm

3

0 20 40 60 800

20

40

60

80

100CXR9HXR9

days

Per

cen

t su

rviv

al

p=0.004

p<0.001

CXR9

HXR90.0

0.2

0.4

0.6

cFo

s ex

pre

ssio

n

p=0.0027

CXR9 HXR9

S

T

d

Online resource 1

CXCL1 5.13

FOSB 4.04ATF3 3.61AREG 3.61TNFAIP3 3.70NR4A21 3.32NR4A3 3.08ZFP36 3.07CD83 2.73UPP1 2.53

PPP1R15A 2.82

CD86 2.73CCL20 2.37EGR1 2.65ARL14 2.24TNF 3.21KLF2 2.07DUSP5 2.26IL1RL1 1.86NCOA7 2.46

4 5 6 7 8 9

0250500750100012501500

*

TGATTAAT(G/T)(G/A)

Online resource 2

Log fold increase in transcription by

HXR9

Base pairs 5’ from transcription start site

Muco

id

Lobular

Ductal

0

100

200

300

400

500M

ean

exp

HO

XB

1to

B9

<5ye

ars

>5ye

ars

0

200

400

600

800

1000

Mea

n e

xp H

OX

B1t

oB

9

ER-ER+

0

200

400

600

800

Mea

n e

xp H

OX

B1t

oB

9

G2 G30

200

400

600

Mea

n e

xp H

OX

B1t

oB

9

No nodes

Nodes0

500

1000

1500

Mea

n e

xp H

OX

B1t

oB

9

Left

Right

0

200

400

600

800

1000

Mea

n e

xp H

OX

B1t

oB

9

a

b

c

d

e

f

Online resource 3

p=

0.0

12

6

p=

0.0

17

0

p=0.3488

p=0.8836 p=0.9754

p=0.2378 p=0.0688

HER2-

HER2+0

200

400

600

800

1000

Mea

n e

xp H

OX

B1t

oB

9

PR-PR+

0

200

400

600

800

Mea

n e

xp H

OX

B1t

oB

9

h

g

p=0.7544

p=0.8344