Expression of vascular endothelial growth factor receptors and invasion and metastasis of hepatocellular carcinoma
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摘要: 血管内皮生长因子受体(VEGFR)含3种受体酪氨酸激酶(RTK)超家族成员和2种非RTK超家族成员,其与配体以非一一对应形式相互结合,通过细胞表面受体内化作用介导Raf1→MAP2K1/2→ERK1/2等多条信号传导通路,引起肝癌细胞增殖和血管、淋巴管生成。VEGFR在肝癌患者局部癌灶高表达,是介导肝细胞癌恶性增生、侵袭转移的关键因素,与患者无进展生存期呈负相关。基质金属蛋白酶-9、热休克蛋白90β可上调VEGFR促进肝癌细胞增殖转移,而miR-203a、miR-378a、miR-199a-3p等可下调VEGFR表达抑制肝癌细胞浸润。基于VEGFR靶向药物治疗可诱导肝癌细胞凋亡,阻断肿瘤血管新生,延缓患者病情进展。
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关键词:
- 受体,血管内皮生长因子 /
- 癌,肝细胞 /
- 肿瘤形成过程
Abstract: Vascular endothelial growth factor receptors ( VEGFRs) consist of three receptor tyrosine kinase ( RTK) superfamily members and two non-RTK superfamily members and bind to the ligand in a non-one-to-one way. VEGFRs mediate various signaling pathways such as Raf1→MAP2 K1/2→ERK1/2 through cell surface receptor internalization and thus promote the proliferation of hepatocellular carcinoma cells, angiogenesis, and lymphangiogenesis. VEGFRs can be highly expressed in local cancerous lesions of liver cancer patients, which is a key factor mediating malignant proliferation, invasion, and metastasis of hepatocellular carcinoma, and the expression of VEGFRs is negatively correlated with progression-free survival. Matrix metalloproteinase-9 and heat shock protein 90β can upregulate VEGFRs to promote the proliferation and metastasis of hepatoma cells, while miR-203 a, miR-378 a, and miR-199 a-3 p can downregulate VEGFR expression and inhibit hepatoma cell infiltration. Targeted drug therapy based on VEGFR can induce the apoptosis of hepatoma cells, block tumor angiogenesis, and delay disease progression. -
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