The expression of Cullin1 is increased in renal cell carcinoma and promotes cancer cell proliferation, migration, and invasion
The expression of Cullin1 is increased in renal cell carcinoma and promotes cancer cell proliferation, migration, and invasion
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Cullin1在肾细胞癌中表达增加并促进癌细胞增殖、迁移和侵袭
DOI：
10.1007/s13277-016-5151-6
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发表时间：
2016-09-01
期刊：
影响因子：
--
通讯作者：
Zheng, Jun-Nian
中科院分区：
文献类型：
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作者：
Ping, Ji-Gen;Wang, Fei;Zheng, Jun-Nian
Cullin1(Cul1)是泛素E3连接酶Skp1/cullin1/Rbx1/F-box蛋白复合体的支架蛋白，它泛化了细胞周期进程、信号转导和转录等多种蛋白质。为探讨cul1在肾癌发生发展中的作用，采用免疫组织化学方法检测了307例肾癌组织和34例正常肾组织中cul1的表达。肾细胞癌组织中CUL1的表达显著升高，并与肾癌组织学分级(P=0.007)、肿瘤大小(P=0.013)、肾癌状态(P=0.023)相关。此外，我们还发现，沉默cul1导致p21和p27表达增加，这可能抑制细胞周期蛋白D1和细胞周期蛋白E2的表达，并使细胞周期停滞在G1期。此外，通过上调TIMP-1的表达来抑制基质金属蛋白酶-9的表达，从而抑制肾癌细胞的迁移和侵袭能力。最后，利用生物发光成像技术，我们发现在体内，基因敲除的cul1基因显著降低了肿瘤的生长。CUL1可能成为肾细胞癌潜在的治疗靶点。
Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cul1 in the development of renal cell carcinoma (RCC), we evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) containing 307 cases of RCC tissues and 34 normal renal tissues. The Cul1 expression was increased significantly in RCC and was correlated with renal carcinoma histology grade (P= 0.007), tumor size (P= 0.013), and pT status (P= 0.023). Also, we found that silencing of Cul1 leads to increased expression of p21 and p27 that could inhibit the cyclin D1and cyclin E2expressions and arrest cell cycle at the G1 phase. Furthermore, knockdown of Cul1 inhibits RCC cell migration and invasion abilities by up-regulating the expression of TIMP-1 which could inhibit the expression of MMP-9. Finally, using bioluminescence imaging, we found that Cul1 knockdown significantly reduced the tumor growth in vivo. Cul1 may constitute a potential therapeutic target in RCC.