Shi Ameng, Wang Ting, Jia Miao, Dong Lei, Shi Haitao
Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Front Genet. 2021 Nov 9;12:760048. doi: 10.3389/fgene.2021.760048. eCollection 2021.
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.
我们在先前的研究中发现，SDF-1/CXCR7轴在胃癌的生长和增殖中发挥重要作用。本研究的目的是探讨SDF-1/CXCR7对胃癌细胞转移能力的影响及可能机制。通过慢病毒载体稳定敲低SGC-7901胃癌细胞中的CXCR7表达。采用Transwell迁移和侵袭实验检测细胞迁移和侵袭能力。用实时PCR和/或蛋白质印迹法检测基质金属蛋白酶2（MMP-2）、MMP-9、血管内皮生长因子（VEGF）、上皮-间质转化（EMT）标志物的表达及Akt磷酸化水平。我们发现，SDF-1显著增强SGC-7901胃癌细胞的迁移和侵袭能力；敲低CXCR7可抑制这些作用。SDF-1/CXCR7增加MMP-2、MMP-9和VEGF的表达。SDF-1/CXCR7还下调E-钙黏蛋白表达，但上调N-钙黏蛋白、波形蛋白和Snail表达，提示SDF-1/CXCR7可促进胃癌细胞的EMT进程。此外，SDF-1/CXCR7可促进Akt磷酸化。我们的结果表明，SDF-1/CXCR7增强胃癌细胞的迁移、侵袭及EMT，因此抑制CXCR7可能是抑制胃癌转移的一种策略。
