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c-Myc 通过调节 HIF-1α 增强结肠癌细胞介导的血管生成。

c-Myc enhances colon cancer cell-mediated angiogenesis through the regulation of HIF-1α.

机构信息

Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Biochem Biophys Res Commun. 2013 Jan 11;430(2):505-11. doi: 10.1016/j.bbrc.2012.12.006. Epub 2012 Dec 10.

Abstract

Angiogenesis plays a pivotal role in tumor growth. The hypoxia-inducible factor 1, α subunit (HIF-1α)/vascular endothelial growth factor pathway is the most important pathway for regulating angiogenesis in the tumor microenvironment. c-Myc is an important oncogene that has many biological functions. In this study, we investigated the role of c-Myc in tumor angiogenesis. We found that the overexpression of c-Myc in colon cancer cells could promote the expression of HIF-1α and that of vascular endothelial growth factor. Moreover, we found that c-Myc regulated HIF-1α at the post-transcriptional level. The results revealed c-Myc-dependent regulation of HIF-1α instead of HIF-1α-dependent c-Myc regulation for the first time. They also showed that c-Myc was essential to regulate colon cancer cell-mediated angiogenesis and contributed to tumor growth. This research provides the theoretical basis for clinical trials of new therapeutic targets of c-Myc and HIF-1α in colon cancer cells.

摘要

血管生成在肿瘤生长中起着关键作用。缺氧诱导因子 1,α 亚基(HIF-1α)/血管内皮生长因子途径是调节肿瘤微环境中血管生成的最重要途径。c-Myc 是一种重要的癌基因,具有许多生物学功能。在这项研究中,我们研究了 c-Myc 在肿瘤血管生成中的作用。我们发现,结肠癌细胞中 c-Myc 的过表达可以促进 HIF-1α 和血管内皮生长因子的表达。此外,我们发现 c-Myc 在转录后水平调节 HIF-1α。结果首次揭示了 c-Myc 对 HIF-1α 的依赖性调节,而不是 HIF-1α 对 c-Myc 的依赖性调节。它们还表明,c-Myc 对于调节结肠癌细胞介导的血管生成和促进肿瘤生长是必不可少的。这项研究为临床研究结肠癌中 c-Myc 和 HIF-1α 的新治疗靶点提供了理论依据。

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