J Cancer Prev.  2018 Mar;23(1):1-9. 10.15430/JCP.2018.23.1.1.

Identification of Epithelial-Mesenchymal Transition-related Target Genes Induced by the Mutation of Smad3 Linker Phosphorylation

• 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

• KMID: 2416946
• DOI: http://doi.org/10.15430/JCP.2018.23.1.1

Abstract

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-β1 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.

Keyword

Smad3; Epithelial-mesenchymal transition; Pancreatic cancer; Prostate cancer; RNA sequence analysis

MeSH Terms

Breast Neoplasms
Cell Line
Cell Movement
Epithelial-Mesenchymal Transition
Humans
Lung
Neoplasm Metastasis
Pancreatic Neoplasms
Phosphorylation*
Phosphotransferases
Prostatic Neoplasms
Sequence Analysis, RNA
Phosphotransferases