C23 protein meditates bone morphogenetic protein-2-mediated EMT via up-regulation of Erk1/2 and Akt in gastric cancer.

Abstract

In our previous study, the epithelial-to-mesenchymal transition (EMT) has been identified to be involved in gastric cancer progression. Notably, nuclear protein C23 and bone morphogenetic protein-2 (BMP2) have been linked into EMT. However, the specific mechanisms underlying BMP2 pathway-mediated EMT are not still unraveled. In this study, we adopted immunohistochemistry and immunoblotting to determine the expression of C23 and BMP2 receptor II (BMPR-II) in 90 gastric cancer samples and cell lines. Subsequently, relevant cell lines were selected to be treated with si-C23 or si-BMPRII and the detection of in vitro assay. Our results revealed that both C23 and BMPRII were aberrantly and constitutively expressed in gastric cancer specimens and cell lines, whose expression was positively associated with metastasis, stage and differentiation, and portended poor survival outcome of gastric cancer patients. In vitro assay validated the increased expression of p-Erk1/2, p-Akt, vimentin, N-cadherin, and MMP2 in BMP2-stimulated MGC803 cells, which was in a dose-dependent manner. By contrast, si-C23 treatment attenuated the BMP2-stimulated expression of p-Erk1/2, p-Akt, vimentin, N-cadherin, and MMP2. Also, the treatment of either si-C23 or si-BMPRII decreased the ability of migration and invasion of MGC803 cells. In conclusion, C23 mediates BMP2-induced EMT progression via the up-regulation of Erk1/2 and Akt signaling pathway in gastric cancer, which indicated both C23 and BMPRII pathway could be recommended as prospective targets or biomarkers to antagonize the progression of gastric cancer.

• Authors: Yonggang Yang, Chunyan Yang, Jianping Zhang
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 32 Issue 3 Pg. 76 (Mar 2015) ISSN: 1559-131X [Electronic] United States
• PMID: 25698539 (Publication Type: Journal Article)

Chemical References

• BMP2 protein, human
• Bone Morphogenetic Protein 2
• Phosphoproteins
• RNA-Binding Proteins
• nucleolin
• Proto-Oncogene Proteins c-akt
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• BMPR2 protein, human
• Bone Morphogenetic Protein Receptors, Type II

Topics

• Aged
• Bone Morphogenetic Protein 2 (metabolism, pharmacology)
• Bone Morphogenetic Protein Receptors, Type II (metabolism)
• Cell Line, Tumor
• Cell Movement (genetics)
• Epithelial-Mesenchymal Transition
• Female
• Gene Knockdown Techniques
• Humans
• Male
• Middle Aged
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Phosphoproteins (genetics, metabolism)
• Prognosis
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA-Binding Proteins (genetics, metabolism)
• Stomach Neoplasms (metabolism, mortality, pathology)
• Up-Regulation