β-catenin stabilization enhances SS18-SSX-driven synovial sarcomagenesis

and drives an epithelial-mesenchymal transition

CTOS 2014 ■ Berlin, Germany

Kevin B. Jones, Benjamin E. Illum,

Huifeng Jin, Ju-Fen Zhu,

Michael J. Monument, Mario R. Capecchi

No financial disclosures

SARCOMAGENESIS

β-catenin

SS18-SSX2

mon

opha

sic

biph

asic

β-

catenin

GSK-3β

APC β-catenin

P

β-catenin

P

nucleus

adherensjunction

transcription

con

dit

ion

ally

ac

tiva

ted

SS18-SSX2

con

dit

ion

ally

st

abili

zed

Ctnnb1

8 weeksfollowinginjection of AdCre

Rosa26-hSS2/wt+Ctnnb1-ex3fl/wt

m

Enabled different cell of origin?

or

Blocked epithelial differentiation by EMT?

Cyt Nuc Cyt Nuc

Ctnnb1-ex3fl Ctnnb1-wt tumor tumor

Chip-qPCR from Mouse SSM2 Tumor5/5/14_JZ

ChIP Antibody

Fo

ld E

nri

ch

me

nt

Input BRM b-catenin 0

5

10

15

20 m_cyclin D1_prom_cyclin D1_pro P3m_cyclin D1_pro P4

Chip-qPCR from Mouse SSM2 Tumor5/5/14_JZ

ChIP Antibody

Fo

ld E

nri

ch

me

nt

Input BRM b-catenin 0

2

4

6

8

10

30

40

50

60

70 m_Myc_pro P1m_Myc_pro P2

ChIP in a Ctnnb1-wt tumor still finds β-catenin at the Myc and Ccnd1 promoters

CreTAT

hSS2/Ctnnb1-ex3flhSS2/Ctnnb1-wt

hSS2/Ctnnb1-ex3flhSS2/Ctnnb1-wt

β-catenin

SARCOMAGENESIS

β-catenin

SS18-SSX2

mon

opha

sic

biph

asic

Thank You!