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!
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