title: The expression of Cullin1 is increased in renal cell carcinoma and promotes cancer cell proliferation, migration, and invasion.
abstract: 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.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China.
authors.forename: Ji-Gen
authors.initials: JG
authors.lastname: Ping
authors.affiliation: Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China.
authors.forename: Jin-Xian
authors.initials: JX
authors.lastname: Pu
authors.affiliation: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, Jiangsu Province, 221002, China.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China.
authors.forename: Ping-Fu
authors.initials: PF
authors.lastname: Hou
authors.affiliation: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, Jiangsu Province, 221002, China.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China.
authors.forename: Yan-Su
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, Jiangsu Province, 221002, China. bj@xzmc.edu.cn.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China. bj@xzmc.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Bai
authors.affiliation: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, Jiangsu Province, 221002, China. jnzheng@xzmc.edu.cn.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China. jnzheng@xzmc.edu.cn.
authors.forename: Jun-Nian
authors.initials: JN
authors.lastname: Zheng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology*; D044842:Cullin Proteins / Q000096:biosynthesis* / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D046888:Tissue Array Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C100318:Cullin 1; D044842:Cullin Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019715:Tissue Inhibitor of Metalloproteinase-1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020780:Matrix Metalloproteinase 9
keywords: Cell progression; Cullin1; Renal cell carcinoma; Tissue microarray