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2017 ; 8
(24
): 39401-39416
Nephropedia Template TP
gab.com Text
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English Wikipedia
OVOL2 antagonizes TGF-? signaling to regulate epithelial to mesenchymal
transition during mammary tumor metastasis
#MMPMID28455959
Wu RS
; Hong JJ
; Wu JF
; Yan S
; Wu D
; Liu N
; Liu QF
; Wu QW
; Xie YY
; Liu YJ
; Zheng ZZ
; Chan EC
; Zhang ZM
; Li BA
Oncotarget
2017[Jun]; 8
(24
): 39401-39416
PMID28455959
show ga
Great progress has been achieved in the study of the role of TGF-? signaling in
triggering epithelial-mesenchymal transition (EMT) in a variety of cancers;
however, the regulation of TGF-? signaling during EMT in mammary tumor metastasis
has not been completely defined. In the present study, we demonstrated that
OVOL2, a zinc finger transcription factor, inhibits TGF-? signaling-induced EMT
in mouse and human mammary tumor cells, as well as in mouse tumor models. Data
from the Oncomine databases indicated a strong negative relationship between
OVOL2 expression and breast cancer progression. Moreover, our experiments
revealed that OVOL2 inhibits TGF-? signaling at multiple levels, including
inhibiting Smad4 mRNA expression and inducing Smad7 mRNA expression, blocking the
binding between Smad4 and target DNA, and interfering with complex formation
between Smad4 and Smad2/3. These findings reveal a novel mechanism that controls
the TGF-? signaling output level in vitro and in vivo. The modulation of these
molecular processes may represent a strategy for inhibiting breast cancer
invasion by restoring OVOL2 expression.