title: High-level expression of Notch1 increased the risk of metastasis in T1 stage clear cell renal cell carcinoma.
abstract: BACKGROUND
  Although metastasis of clear cell renal cell carcinoma (ccRCC) is basically observed in late stage tumors, T1 stage metastasis of ccRCC can also be found with no definite molecular cause resulting inappropriate selection of surgery method and poor prognosis. Notch signaling is a conserved, widely expressed signal pathway that mediates various cellular processes in normal development and tumorigenesis. This study aims to explore the potential role and mechanism of Notch signaling in the metastasis of T1 stage ccRCC.
  
  
  RESULTS
  The expression of Notch1 and Jagged1 were analyzed in tumor tissues and matched normal adjacent tissues obtained from 51 ccRCC patients. Compared to non-tumor tissues, Notch1 and Jagged1 expression was significantly elevated both in mRNA and protein levels in tumors. Tissue samples of localized and metastatic tumors were divided into three groups based on their tumor stages and the relative mRNA expression of Notch1 and Jagged1 were analyzed. Compared to localized tumors, Notch1 expression was significantly elevated in metastatic tumors in T1 stage while Jagged1 expression was not statistically different between localized and metastatic tumors of all stages. The average size of metastatic tumors was significantly larger than localized tumors in T1 stage ccRCC and the elevated expression of Notch1 was significantly positive correlated with the tumor diameter. The functional significance of Notch signaling was studied by transfection of 786-O, Caki-1 and HKC cell lines with full-length expression plasmids of Notch1 and Jagged1. Compared to the corresponding controls, all cell lines demonstrated significant promotion in cell proliferation and migration while cell cycle remained unaffected.
  
  
  CONCLUSIONS
  High-level expression of Notch signaling increased the risk of metastasis in T1 stage ccRCC by stimulating the proliferation and migration of tumor cells, which may be helpful for the selection of suitable operation method and prognosis of ccRCC.
authors.affiliation: Medical School, Nankai University, Tianjin, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ai
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Huang
authors.forename: Shangwen
authors.initials: S
authors.lastname: Liu
authors.forename: Taoping
authors.initials: T
authors.lastname: Shi
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Mingyang
authors.initials: M
authors.lastname: Zhu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Baojun
authors.initials: B
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Ni
authors.forename: Hongzhao
authors.initials: H
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Zheng
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D051881:Receptor, Notch1 / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D012333:RNA, Messenger; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins