title: Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior.
abstract: The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA. Chromatin immunoprecipitation and NNMT promoter luciferase assays revealed that AURKA's effects on NNMT were caused by PAX3-mediated transcriptional repression and overexpression of NNMT blocked tumor cell invasion in vitro. Overexpression of AURKA and activation of its downstream pathway was enriched in the basal subtype in primary human tumors and was associated with poor clinical outcomes. We also show that the FISH test for the AURKA gene copy number in urine yielded a specificity of 79.7% (95% confidence interval [CI] = 74.2% to 84.1%), and a sensitivity of 79.6% (95% CI = 74.2% to 84.1%) with an AUC of 0.901 (95% CI = 0.872 to 0.928; P < 0.001). These results implicate AURKA as an effective biomarker for bladder cancer detection as well as therapeutic target especially for its basal type.
authors.affiliation: Department of Cancer Biology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Mobley
authors.affiliation: Department Pathology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Shizhen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department Pathology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Bondaruk
authors.affiliation: Department Pathology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department Pathology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Majewski
authors.affiliation: Department Pathology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Caraway
authors.affiliation: Department of Cancer Biology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Cancer Biology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Einav
authors.initials: E
authors.lastname: Shoshan
authors.affiliation: Department of Cancer Biology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Guermarie
authors.initials: G
authors.lastname: Velazquez-Torres
authors.affiliation: Department of Cancer Biology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Nitti
authors.affiliation: Department Pathology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Sangkyou
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department Pathology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: June Goo
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Department Pathology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Enrique
authors.initials: E
authors.lastname: Fuentes-Mattei
authors.affiliation: Department Urology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Willis
authors.affiliation: Department Bioinformatics &Comp Biology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cancer Biology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Guo
authors.affiliation: Department Bioinformatics &Comp Biology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department Bioinformatics &Comp Biology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Baggerly
authors.affiliation: Department of Urology, UT Southwestern University, Dallas, TX 75390, USA.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, TS 77030, USA.
authors.forename: Seth P
authors.initials: SP
authors.lastname: Lerner
authors.affiliation: Department Urology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Dinney
authors.affiliation: Department Urology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: David
authors.initials: D
authors.lastname: McConkey
authors.affiliation: Department of Cancer Biology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Menashe
authors.initials: M
authors.lastname: Bar-Eli
authors.affiliation: Department Pathology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Czerniak
mesh_terms: D064096:Aurora Kinase A / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D055088:Early Detection of Cancer; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D011379:Prognosis; D014158:Transcription, Genetic; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D064096:Aurora Kinase A