RETRACTED ARTICLE: SDF-1/CXCR4 Axis Regulates Cell Cycle Progression and Epithelial-Mesenchymal Transition via Up-regulation of Survivin in Glioblastoma

Abstract

Stromal cell-derived factor 1 (SDF-1)/CXCR4 ligand-receptor axis is widely recommended as an attractive target for cancer therapy. Meanwhile, epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. As one of inhibitors of apoptosis proteins, survivin is implicated in the onset and development of cancer. In the present study, we tried to determine the cause-effect associations between SDF-1/CXCR4 axis and survivin expression in glioblastoma U-251 cell line. Survivin activation and inhibition were induced with exogenous SDF-1 and survivin small interfering RNA (survivin siRNA), respectively. Western blot was used to detect relevant proteins in SDF-1/CXCR4 axis. Western blot analysis revealed that survivin expression in U-251 increased in a dose- and time-dependent manner in response to SDF-1 treatment. However, the interference with MEK/ERK and PI3K/AKT pathway prohibited SDF-1-induced survivin up-regulation. Importantly, survivin knockdown abrogated cell cycle progression and the expression of snail and N-cadherin, compared with non-transfectants. In conclusion, the present study shows that SDF-1 up-regulates survivin via MEK/ERK and PI3K/AKT pathway, leading to cell cycle progression and EMT occurrence dependent on survivin. The blockade of survivin will allow for the treatment of glioblastoma.

Epithelial‐to‐mesenchymal transition transcription factors in cancer‐associated fibroblasts

“…In gastric cancers, IL6 activates fibroblastic Twist1, and the resulting CAFs secrete the chemokine CXCL12 in a Twist1-dependent manner (Lee et al, 2015). Although CXCL12 promotes the expression of Snail1 (Liao et al, 2016;Lv et al, 2015) and Twist1 (Yao et al, 2016) in glioblastoma cancer cells, and of Snail1 in human oral squamous cell carcinomas (Taki et al, 2008), no reports show CXCL12-induced expression of Snail1 or Twist1 in tumour cells of gastric cancers. However, CAFs expressing EMT-TFs can also promote the expression of EMT-TFs in adjacent epithelial cells by increasing the stroma rigidity (Fig.…”

CXCR4 knockdown inhibits the growth and invasion of nasopharyngeal cancer stem cells

“…Zeng et al (32) demonstrated that functional inhibition of CXCR4 lead to suppression of the AKT signal. Liao et al (25) also reported that the cell cycle regulation function of CXCR4 is associated with the AKT signal. Luo et al (4) revealed that CXCR4 activated the AKT signal and promoted the motility of nasopharyngeal carcinoma cells.…”

“…The cell cycle and cell apoptosis are important events that have crucial effects on cell growth. Liao et al (25) demonstrated that CXCR4 regulated the protein level of cyclin and cyclin dependent kinase, thus influencing the cell cycle process. CXCR4 shRNA also showed an anti-apoptotic role in CD133 + nasopharyngeal cancer cells in the present study.…”

“…Epigenetic silencing of CXCR4 promotes loss of cell adhesion in cervical cancer (28). CXCR4 has an influence on the epithelial-to-mesenchymal transition process, regulating the expression of E-cadherin, N-cadherin, and vimentin (25,29). CXCR4 signaling also has an influence on actin polymerization and cell skeleton rearrangement, thus regulating cellular migration (30,31).…”

“…The present study identified that the AKT signal was involved in the regulatory function of CXCR4 in nasopharyngeal cancer stem cells, which is consistent with the report of Luo et al . In addition, mitogen activated protein kinase and nuclear factor κΒ signals have also been revealed to be involved in the regulation mechanism of CXCR4 (4,25,32–34). …”