Identification of Epithelial-Mesenchymal Transition-related Target Genes Induced by the Mutation of Smad3 Linker Phosphorylation
- Author:
Sujin PARK
1
;
Kyung Min YANG
;
Yuna PARK
;
Eunji HONG
;
Chang Pyo HONG
;
Jinah PARK
;
Kyoungwha PANG
;
Jihee LEE
;
Bora PARK
;
Siyoung LEE
;
Haein AN
;
Mi Kyung KWAK
;
Junil KIM
;
Jin Muk KANG
;
Pyunggang KIM
;
Yang XIAO
;
Guangjun NIE
;
Akira OOSHIMA
;
Seong Jin KIM
Author Information
- Publication Type:Original Article
- Keywords: Smad3; Epithelial-mesenchymal transition; Pancreatic cancer; Prostate cancer; RNA sequence analysis
- MeSH: Breast Neoplasms; Cell Line; Cell Movement; Epithelial-Mesenchymal Transition; Humans; Lung; Neoplasm Metastasis; Pancreatic Neoplasms; Phosphorylation; Phosphotransferases; Prostatic Neoplasms; Sequence Analysis, RNA
- From:Journal of Cancer Prevention 2018;23(1):1-9
- CountryRepublic of Korea
- Language:English
- 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.
