title: The involvement of anterior gradient 2 in the stromal cell-derived factor 1-induced epithelial-mesenchymal transition of glioblastoma.
abstract: 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.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, No. 17, Yongwaizheng Street, Jiangxi, 330006, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, No. 17, Yongwaizheng Street, Jiangxi, 330006, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, No. 17, Yongwaizheng Street, Jiangxi, 330006, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, No. 17, Yongwaizheng Street, Jiangxi, 330006, China.
authors.forename: Changgui
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, No. 17, Yongwaizheng Street, Jiangxi, 330006, China.
authors.forename: Shengze
authors.initials: S
authors.lastname: Deng
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, No. 17, Yongwaizheng Street, Jiangxi, 330006, China.
authors.forename: Suyue
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, No. 17, Yongwaizheng Street, Jiangxi, 330006, China. zengermingncm@163.com.
authors.forename: Erming
authors.initials: E
authors.lastname: Zeng
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism
chemical_list: C502296:AGR2 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D051057:Proto-Oncogene Proteins c-akt
keywords: AGR2; EMT; Glioblastoma; SDF-1