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Published on: June 23, 2023
Effects of SDF-1/CXCR7 on the Migration, Invasion and Epithelial-Mesenchymal Transition of Gastric Cancer Cells
Ameng Shi1, Ting Wang2, Miao Jia2
1Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Abstract:
We found that SDF-1/CXCR7 axis played an important role in the growth and proliferation of gastric cancer in the previous studies. The objectives of this study were to explore the effects of SDF-1/CXCR7 on the metastatic ability of gastric cancer cells and the possible mechanisms. CXCR7 expression in SGC-7901 gastric cancer cells was stably knocked down via lentiviral vectors. The cell migration and invasion abilities were detected by transwell migration and invasion assays. The expressions of matrix metalloproteinase 2 (MMP-2), MMP-9, vascular endothelial growth factor (VEGF), epithelial-mesenchymal transition (EMT) markers and Akt phosphorylation were detected with real-time PCR and/or western blot. We found that SDF-1 markedly enhanced the migration and invasion abilities of SGC-7901 gastric cancer cells; CXCR7 knockdown inhibited these effects. SDF-1/CXCR7 increased the expressions of MMP-2, MMP-9 and VEGF. SDF-1/CXCR7 also downregulated E-cadherin expression but upregulated N-cadherin, vimentin and Snail expressions, suggesting that SDF-1/CXCR7 could promote the development of EMT in gastric cancer cells. Furthermore, SDF-1/CXCR7 could promote Akt phosphorylation. Our results indicated that SDF-1/CXCR7 enhanced the migration, invasion and EMT of gastric cancer cells and thus CXCR7 supression may be a strategy for inhibiting gastric cancer metastasis.
Insights
The stromal-derived factor 1 (SDF-1)/CXCR7 axis promotes gastric cancer metastasis by enhancing cell migration, invasion, and epithelial-mesenchymal transition (EMT). Suppressing CXCR7 may inhibit gastric cancer spread.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Previous studies identified the SDF-1/CXCR7 axis's role in gastric cancer growth and proliferation.
- The impact of SDF-1/CXCR7 on gastric cancer cell metastasis and underlying mechanisms required further investigation.
Purpose of the Study:
- To investigate the effects of the SDF-1/CXCR7 axis on the metastatic potential of gastric cancer cells.
- To elucidate the molecular mechanisms by which SDF-1/CXCR7 influences gastric cancer cell invasion and migration.
Main Methods:
- Stable knockdown of CXCR7 in SGC-7901 gastric cancer cells using lentiviral vectors.
- Assessment of cell migration and invasion via Transwell assays.
- Analysis of matrix metalloproteinase (MMP-2, MMP-9), vascular endothelial growth factor (VEGF), epithelial-mesenchymal transition (EMT) markers, and Akt phosphorylation using real-time PCR and Western blot.
Main Results:
- SDF-1 significantly increased gastric cancer cell migration and invasion, while CXCR7 knockdown attenuated these effects.
- SDF-1/CXCR7 axis upregulated MMP-2, MMP-9, and VEGF expression.
- SDF-1/CXCR7 promoted epithelial-mesenchymal transition (EMT) by downregulating E-cadherin and upregulating N-cadherin, vimentin, and Snail.
- SDF-1/CXCR7 enhanced Akt phosphorylation.
Conclusions:
- The SDF-1/CXCR7 axis plays a crucial role in enhancing gastric cancer cell migration, invasion, and EMT.
- CXCR7 suppression presents a potential therapeutic strategy to inhibit gastric cancer metastasis.
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