SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin (Retracted Article)
SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin (Retracted Article)
复制标题
SARI通过直接靶向铜蓝蛋白抑制人结肠癌的血管生成和肿瘤生长
DOI：
10.1038/ncomms11996
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发表时间：
2016-06-01
影响因子：
16.6
通讯作者：
Deng, Hongxin
中科院分区：
文献类型：
--
作者：
Dai, Lei;Cui, Xueliang;Deng, Hongxin
SARI，也被称为BATF2，属于BATF家族，与抑制癌细胞生长有关。然而，SARI在肿瘤血管生成中的作用和机制尚不清楚。在这里，我们证明SARI缺乏促进AOM/DSS诱导的小鼠结肠肿瘤的发生。我们发现SARI是一种新型的抑制小鼠结肠肿瘤生长和血管生成的药物。抗体阵列和HUVEC相关检测表明，血管内皮生长因子在SARI控制的血管生成抑制中具有重要作用。此外，Co-IP/PAGE/MS分析表明，SARI直接靶向铜蓝蛋白(CP)，并诱导CP的蛋白酶降解，从而抑制HIF-1α/VEGF轴的活性。组织芯片结果显示，在结肠癌患者中，sARI的表达与不良的临床结果呈负相关。总而言之，我们的结果表明SARI是一个潜在的治疗靶点，它通过减少血管内皮生长因子的表达来抑制血管生成，并且是结肠癌患者的预后指标。
SARI, also called as BATF2, belongs to the BATF family and has been implicated in cancer cell growth inhibition. However, the role and mechanism of SARI in tumour angiogenesis are elusive. Here we demonstrate that SARI deficiency facilitates AOM/DSS-induced colonic tumorigenesis in mice. We show that SARI is a novel inhibitor of colon tumour growth and angiogenesis in mice. Antibody array and HUVEC-related assays indicate that VEGF has an essential role in SARI-controlled inhibition of angiogenesis. Furthermore, Co-IP/PAGE/mass spectrometry indicates that SARI directly targets ceruloplasmin (Cp), and induces protease degradation of Cp, thereby inhibiting the activity of the HIF-1α/VEGF axis. Tissue microarray results indicate that SARI expression inversely correlates with poor clinical outcomes in colon cancer patients. Collectively, our results indicate that SARI is a potential target for therapy by inhibiting angiogenesis through the reduction of VEGF expression and is a prognostic indicator for patients with colon cancer.