title: The effect of Aurora kinases on cell proliferation, cell cycle regulation             and metastasis in renal cell carcinoma.
abstract: Aurora kinases have been shown to be involved in the regulation of the cell             cycle and are related to tumor progression. This suggests the possibility that             they can serve as new anticancer targets for tumor treatment. However, the important             roles that Aurora kinases and their signaling pathway play in renal cell carcinoma             (RCC) are not fully understood and addressed to date. In this study, we aimed             to address these questions. We observed that downregulation of Aurora kinases             induced by AurA miRNA, AurB miRNA or VX680 could inhibit proliferation and metastasis,             induce G2/M phase arrest in clear cell renal cell carcinoma cells and exert antitumor             activity in an SN12C xenograft model. We also show that either silencing of Aurora             kinases or treating the cells with VX680 could downregulate the expression of             cdc25c and cyclin B/cdc2, upregulate the expression of p-cdc2 (Tyr15) via blocking             the activity of ERK. All these changes may contribute to inhibition of proliferation,             metastasis and G2/M arrest in ccRCC. In summary, we proved that both Aurora kinases             A and B are key elements of tumor growth regulation, and inhibition of Aurora             kinases may contribute to blocking ccRCC progression. We conclude that Aurora             kinases could be potential therapeutic targets in the management of renal cell             carcinoma.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Wanqi
authors.initials: W
authors.lastname: Zhou
authors.forename: Langli
authors.initials: L
authors.lastname: Wei
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D064127:Aurora Kinases; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines
chemical_list: D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D010879:Piperazines; D017346:Protein Serine-Threonine Kinases; C484810:tozasertib; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines