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

Affiliations
  • 1Precision Medicine Research Center, Advanced Institutes of Convergence Technology, Suwon, Korea. jasonsjkim@snu.ac.kr
  • 2Department of Biomedical Science, College of Life Science, CHA University, CHA Bio Complex, Seongnam, Korea.
  • 3Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
  • 4Theragen Etex Bio Institute, Suwon, Korea.
  • 5CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing, China.
  • 6Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Korea.

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
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