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Updated: Mar 8, 2026
Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
Published on: July 30, 2020
Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior
Aaron Mobley1, Shizhen Zhang2, Jolanta Bondaruk2
1Department of Cancer Biology, The University of Texas at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
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.
Insights
Aurora Kinase A (AURKA) overexpression drives bladder cancer invasion and is linked to poor outcomes. Targeting AURKA and its pathway, particularly in basal subtype bladder cancers, offers a promising therapeutic strategy and detection biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aurora Kinase A (AURKA) overexpression is linked to poor clinical outcomes in bladder cancer, potentially due to cell cycle dysregulation and genomic instability.
- Understanding AURKA's downstream effects is crucial for identifying therapeutic targets and biomarkers.
Purpose of the Study:
- To investigate the role of AURKA in human bladder cancer cell invasion.
- To identify downstream targets of AURKA and their contribution to bladder cancer progression.
- To evaluate AURKA as a diagnostic biomarker for bladder cancer.
Main Methods:
- RNA interference was used to assess the impact of AURKA knockdown on bladder cancer cells.
- Whole genome mRNA expression profiling and chromatin immunoprecipitation identified NNMT as a downstream target of AURKA.
- Fluorescence in situ hybridization (FISH) was employed to analyze AURKA gene copy number in urine samples.
Main Results:
- AURKA knockdown inhibited bladder cancer cell invasion but had minimal effect on proliferation.
- Nicotinamide N-methyltransferase (NNMT) was identified as a downstream target repressed by AURKA, and its overexpression also blocked invasion.
- AURKA overexpression and pathway activation were prevalent in the basal subtype of human bladder tumors, correlating with poor outcomes.
- The FISH test for AURKA gene copy number in urine demonstrated high diagnostic accuracy (AUC=0.901).
Conclusions:
- AURKA plays a significant role in bladder cancer cell invasion, partly through the repression of NNMT.
- AURKA is a potential therapeutic target, especially for the basal subtype of bladder cancer.
- AURKA serves as a valuable biomarker for non-invasive bladder cancer detection.
