The involvement of anterior gradient 2 in the stromal cell-derived factor 1-induced epithelial-mesenchymal transition of glioblastoma
Autor: | Shengze Deng, Li-Min Xiao, Chunhua Xu, Er-Ming Zeng, Changgui Guo, Su-Yue Zheng, Yue Liu |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Receptors CXCR4 Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Stromal cell Cell cycle checkpoint Gene Expression AGR2 CXCR4 03 medical and health sciences Mucoproteins 0302 clinical medicine Cell Movement Cell Line Tumor Humans Medicine Stromal cell-derived factor 1 RNA Messenger Epithelial–mesenchymal transition RNA Small Interfering U87 PI3K/AKT/mTOR pathway Oncogene Proteins biology business.industry Cell Cycle Proteins General Medicine Chemokine CXCL12 030104 developmental biology Gene Knockdown Techniques 030220 oncology & carcinogenesis Cancer research biology.protein Glioblastoma business Proto-Oncogene Proteins c-akt |
Zdroj: | Tumor Biology. 37:6091-6097 |
ISSN: | 1423-0380 1010-4283 |
Popis: | In recent years, it has been widely identified that the stromal cell-derived factor 1 (SDF-1) and anterior gradient 2 (AGR2) were implicated in the development of epithelial-mesenchymal transition (EMT) in a variety of cancers. However, the involvement of SDF-1-AGR2 pathway in the EMT of glioblastoma has not been investigated. In the present study, the in vitro assays were used to investigate the role of AGR2 in cell cycle, migration, and invasion. We found that the expressions of AGR2 and chemokine (C-X-C motif) receptor 4 (CXCR4) were obviously upregulated in glioblastoma cells T98G, A172, U87, and U251 than those in normal human astrocytes (NHA) (all p 0.01), among which both U87 and U251 cells presented the highest expression (p 0.05). Western blot revealed that SDF-1 induced the expression of p-AKT, AGR2, and EMT markers (N-cadherin, matrix metalloproteinase-2 (MMP2), and Slug) in a dose-dependent manner in U87 and U251 cells. However, the depletion of AGR2 reversed SDF-1-induced upregulation of EMT markers rather than p-AKT. Furthermore, functional analysis identified that knockdown of AGR2 induced cell cycle arrest in G0/G1 phase and suppressed the migration and invasion of U87 and U251 cells. Taken together, SDF-1-CXCR4 pathway induced the expression of AGR2 to control the progression of EMT likely via AKT pathway in the development of glioblastoma. Our findings lay a promising foundation for the SDF-1-AGR2 axis-targeting therapy in patients with glioblastoma. |
Databáze: | OpenAIRE |
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