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The anti-proliferative function of the TGF-?1 signaling pathway involves the
repression of the oncogenic TBX2 by its homologue TBX3
#MMPMID25371204
Li J
; Ballim D
; Rodriguez M
; Cui R
; Goding CR
; Teng H
; Prince S
J Biol Chem
2014[Dec]; 289
(51
): 35633-43
PMID25371204
show ga
A growing body of work has shown that the highly homologous T-box transcription
factors TBX2 and TBX3 play critical but distinct roles in embryonic development
and cancer progression. For example, TBX2 and TBX3 are up-regulated in several
cancers and recent evidence suggests that whereas TBX2 functions as a
pro-proliferative factor, TBX3 inhibits cell proliferation but promotes cancer
cell migration and invasion. While the molecular mechanisms regulating these
functions of TBX2 and TBX3 are poorly understood we recently reported that the
TGF-?1 signaling pathway up-regulates TBX3 expression to mediate, in part, its
well described anti-proliferative and pro-migratory roles. The TBX3 targets
responsible for these functions were however not identified. Here we reveal for
the first time that the TGF-?1 signaling pathway represses TBX2 transcriptionally
and we provide a detailed mechanism to show that this is mediated by TBX3.
Furthermore, we implicate the down-regulation of TBX2 in the anti-proliferative
function of the TGF-?1-TBX3 axis. These findings have important implications for
our understanding of the regulation of TBX2 and TBX3 and shed light on the
mechanisms involved in the anti-proliferative and pro-migratory roles of TGF-?1.
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