title: Targeting Aurora Kinase A enhances radiation sensitivity of atypical teratoid rhabdoid tumor cells.
abstract: Atypical teratoid/rhabdoid tumors (ATRT) are rare, highly malignant, embryonal CNS tumors with a poor prognosis. Therapy relies on highly toxic chemotherapy and radiotherapy. To improve outcomes and decrease morbidity, more targeted therapy is required. Gene expression analysis revealed elevated expression of multiple kinases in ATRT tissues. Aurora Kinase A was one of the candidate kinases. The objective of this study was to evaluate the impact of Aurora Kinase A inhibition in ATRT cell lines. Our analysis revealed that inhibition of Aurora Kinase A induces cell death in ATRT cells and the small molecule inhibitor MLN 8237 sensitizes these cells to radiation. Furthermore, inhibition of Aurora Kinase A resulted in decreased activity of pro-proliferative signaling pathways. These data indicate that inhibition of Aurora Kinase A is a promising small molecule target for ATRT therapy.
authors.affiliation: Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Venkataraman
authors.forename: Irina
authors.initials: I
authors.lastname: Alimova
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tello
authors.forename: Peter S
authors.initials: PS
authors.lastname: Harris
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Knipstein
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Donson
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Foreman
authors.forename: Arthur K
authors.initials: AK
authors.lastname: Liu
authors.forename: Rajeev
authors.initials: R
authors.lastname: Vibhakar
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D064096:Aurora Kinase A; D064127:Aurora Kinases; D001381:Azepines / Q000494:pharmacology; D015153:Blotting, Western; D016543:Central Nervous System Neoplasms / Q000201:enzymology* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D018335:Rhabdoid Tumor / Q000201:enzymology* / Q000235:genetics; D013724:Teratoma / Q000201:enzymology* / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001381:Azepines; D004791:Enzyme Inhibitors; C550258:MLN 8237; D011743:Pyrimidines; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases