C23 protein meditates bone morphogenetic protein-2-mediated EMT via up-regulation of Erk1/2 and Akt in gastric cancer
- PMID: 25698539
- DOI: 10.1007/s12032-015-0547-5
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.
Similar articles
-
CrkL meditates CCL20/CCR6-induced EMT in gastric cancer.Cytokine. 2015 Dec;76(2):163-169. doi: 10.1016/j.cyto.2015.05.009. Epub 2015 Jun 1. Cytokine. 2015. PMID: 26044596
-
Bone morphogenetic protein 2 mediates epithelial-mesenchymal transition via AKT and ERK signaling pathways in gastric cancer.Tumour Biol. 2015 Apr;36(4):2773-8. doi: 10.1007/s13277-014-2901-1. Epub 2014 Dec 3. Tumour Biol. 2015. Retraction in: Tumour Biol. 2017 Apr 20. doi: 10.1007/s13277-017-5487-6. PMID: 25448881 Retracted.
-
BMP2 accelerates the motility and invasiveness of gastric cancer cells via activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway.Exp Cell Res. 2010 Jan 1;316(1):24-37. doi: 10.1016/j.yexcr.2009.10.010. Epub 2009 Oct 14. Exp Cell Res. 2010. PMID: 19835871
-
BMP2 as a promising anticancer approach: functions and molecular mechanisms.Invest New Drugs. 2022 Dec;40(6):1322-1332. doi: 10.1007/s10637-022-01298-4. Epub 2022 Aug 30. Invest New Drugs. 2022. PMID: 36040572 Review.
-
Mechanisms of Bone Morphogenetic Protein 2 in Respiratory Diseases.Curr Allergy Asthma Rep. 2024 Oct 28;25(1):1. doi: 10.1007/s11882-024-01181-7. Curr Allergy Asthma Rep. 2024. PMID: 39466470 Review.
Cited by
-
BMP2 inhibits cell proliferation by downregulating EZH2 in gastric cancer.Cell Cycle. 2022 Nov;21(21):2298-2308. doi: 10.1080/15384101.2022.2092819. Epub 2022 Jul 20. Cell Cycle. 2022. PMID: 35856444 Free PMC article.
-
Metastatic pathway-specific transcriptome analysis identifies MFSD4 as a putative tumor suppressor and biomarker for hepatic metastasis in patients with gastric cancer.Oncotarget. 2016 Mar 22;7(12):13667-79. doi: 10.18632/oncotarget.7269. Oncotarget. 2016. PMID: 26872374 Free PMC article.
-
Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling.Cell Death Dis. 2018 Feb 7;9(2):174. doi: 10.1038/s41419-017-0230-1. Cell Death Dis. 2018. PMID: 29416020 Free PMC article.
-
BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway.Aging (Albany NY). 2017 Apr;9(4):1326-1340. doi: 10.18632/aging.101230. Aging (Albany NY). 2017. PMID: 28455969 Free PMC article.
-
The BMP2 Signaling Axis Promotes Invasive Differentiation of Human Trophoblasts.Front Cell Dev Biol. 2021 Feb 4;9:607332. doi: 10.3389/fcell.2021.607332. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 33614644 Free PMC article.
References
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous