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2018 ; 23
(1
): 1-9
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Identification of Epithelial-Mesenchymal Transition-related Target Genes Induced
by the Mutation of Smad3 Linker Phosphorylation
#MMPMID29629343
Park S
; Yang KM
; Park Y
; Hong E
; Hong CP
; Park J
; Pang K
; Lee J
; Park B
; Lee S
; An H
; Kwak MK
; Kim J
; Kang JM
; Kim P
; Xiao Y
; Nie G
; Ooshima A
; Kim SJ
J Cancer Prev
2018[Mar]; 23
(1
): 1-9
PMID29629343
show ga
BACKGROUND: Smad3 linker phosphorylation plays essential roles in tumor
progression and metastasis. We have previously reported that the mutation of
Smad3 linker phosphorylation sites (Smad3-Erk/Pro-directed kinase site mutant
constructs [EPSM]) markedly reduced the tumor progression while increasing the
lung metastasis in breast cancer. METHODS: We performed high-throughput
RNA-Sequencing of the human prostate cancer cell lines infected with adenoviral
Smad3-EPSM to identify the genes regulated by Smad3-EPSM. RESULTS: In this study,
we identified genes which are differentially regulated in the presence of
Smad3-EPSM. We first confirmed that Smad3-EPSM strongly enhanced a capability of
cell motility and invasiveness as well as the expression of
epithelial-mesenchymal transition marker genes, CDH2, SNAI1, and ZEB1 in response
to TGF-?1 in human pancreatic and prostate cancer cell lines. We identified
GADD45B, CTGF, and JUNB genes in the expression profiles associated with cell
motility and invasiveness induced by the Smad3-EPSM. CONCLUSIONS: These results
suggested that inhibition of Smad3 linker phosphorylation may enhance cell
motility and invasiveness by inducing expression of GADD45B, CTGF, and JUNB genes
in various cancers.