Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing, China.
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
Cancer Lett. 2017 Aug 1;400:117-126. doi: 10.1016/j.canlet.2017.04.037. Epub 2017 May 4.
Myocyte enhancer factor 2D (MEF2D) is involved in many aspects of cancer progression, including cell proliferation, invasion, and migration. However, little is known about the role of MEF2D in tumor angiogenesis. Using clinical specimens, colorectal cancer (CRC) cell lines and a mouse model in the present study, we found that MEF2D expression was positively correlated with CD31-positive microvascular density in CRC tissues. MEF2D promoted tumor angiogenesis in vitro and in vivo and induced the expression of proangiogenic cytokines in CRC cells. MEF2D was found to be a downstream effector of hypoxia-inducible factor (HIF)-1α in the induction of tumor angiogenesis. HIF-1α transactivates MEF2D expression by binding to the MEF2D gene promoter. These results demonstrate that the HIF-1α/MEF2D axis can serve as a therapeutic target for the treatment of CRC.
肌细胞增强因子 2D（MEF2D）参与癌症进展的许多方面，包括细胞增殖、侵袭和迁移。然而，MEF2D 在肿瘤血管生成中的作用知之甚少。本研究使用临床标本、结直肠癌细胞系和小鼠模型，发现 MEF2D 表达与 CRC 组织中 CD31 阳性微血管密度呈正相关。MEF2D 促进 CRC 细胞的体外和体内血管生成，并诱导促血管生成细胞因子的表达。发现在诱导肿瘤血管生成中，MEF2D 是缺氧诱导因子 1α（HIF-1α）的下游效应物。HIF-1α 通过与 MEF2D 基因启动子结合来反式激活 MEF2D 表达。这些结果表明，HIF-1α/MEF2D 轴可作为治疗 CRC 的治疗靶点。
