SIX4 激活 Akt 并促进肿瘤血管生成。
SIX4 activates Akt and promotes tumor angiogenesis.
机构信息
GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China; Department of General Surgery, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China.
GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
出版信息
Exp Cell Res. 2019 Oct 1;383(1):111495. doi: 10.1016/j.yexcr.2019.111495. Epub 2019 Jul 10.
Angiogenesis plays important roles in solid tumors progression. Growth factors such as vascular endothelial growth factors (VEGFs) can induce angiogenesis and hypoxia promotes the expression of VEGFs through activating hypoxia-inducible factor 1 (HIF-1α). However, the regulation of HIF-1α still not been fully understood. Here, we demonstrate that the Sine Oculis Homeobox Homolog 4 (SIX4) is up-regulated in colorectal cancer (CRC) and high expression of SIX4 predicts a poor prognosis. Overexpression of SIX4 enhances tumor growth and angiogenesis in vitro and in vivo, while knockdown of SIX4 inhibits tumor growth and angiogenesis. Furthermore, we show that SIX4 increases the expression of VEGF-A by coordinating with the HIF-1α. Mechanically, we explore that SIX4 up-regulates the expression of HIF-1α depending on Akt activation. Collectively, we demonstrate that SIX4 is functional in regulating tumor angiogenesis and SIX4 might be used as anti-angiogenic therapy in CRC.
血管生成在实体肿瘤的进展中起着重要作用。血管内皮生长因子（VEGF）等生长因子可诱导血管生成，而缺氧通过激活缺氧诱导因子 1（HIF-1α）促进 VEGF 的表达。然而，HIF-1α 的调节机制尚不完全清楚。本研究表明，Sine Oculis Homeobox Homolog 4（SIX4）在结直肠癌（CRC）中上调，并且 SIX4 的高表达预示着预后不良。SIX4 的过表达增强了体外和体内的肿瘤生长和血管生成，而 SIX4 的敲低则抑制了肿瘤生长和血管生成。此外，我们还表明，SIX4 通过与 HIF-1α 协同作用增加了 VEGF-A 的表达。从机制上讲，我们探索了 SIX4 依赖 Akt 激活而上调 HIF-1α 的表达。总之，我们证明了 SIX4 在调节肿瘤血管生成方面具有功能，并且 SIX4 可能被用作 CRC 的抗血管生成治疗。
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