Targeting aurora kinase A inhibits hypoxia-mediated neuroblastoma cell tumorigenesis.
OBJECTIVE
It is unknown whether hypoxia regulates aurora kinase A (AURKA), a serine/threonine kinase, in neuroblastoma to stimulate cell growth or migration. We sought to determine whether AURKA mediates hypoxia-induced regulation of neuroblastoma tumorigenicity.


METHODS
Human neuroblastoma BE(2)-C cells were treated with CoCl2, a chemical hypoxia mimetic, and MLN8237, a pharmalogical inhibitor of AURKA, to assess cell viability, colony formation and transwell migration. Focal adhesion kinase (FAK) expression was analyzed after silencing of AURKA under normoxic vs. hypoxic conditions.


RESULTS
Hypoxia up-regulated expression of AURKA mRNA and protein. CoCl2 stimulated cell proliferation and migration, while inhibiting colony formation. MLN8237 reduced colony formation and cell migration. Silencing of AURKA reduced expression of FAK and pFAK under normoxia and hypoxia.


CONCLUSIONS
Hypoxia positively regulates AURKA expression. Hypoxia-induced stimulation of colony formation and migration is, in part, mediated by AURKA. These findings establish that AURKA is a critical regulator of hypoxia-mediated tumor progression in neuroblastoma.
Department of Pediatric Surgery, 2200 Children's Way, DOT 7100, Vanderbilt University Medical Center, Nashville, TN 37232-9780, U.S.A. dai.chung@vanderbilt.edu.
Carmelle V
CV
Romain
Pritha
P
Paul
Sora
S
Lee
Jingbo
J
Qiao
Dai H
DH
Chung
D064096:Aurora Kinase A / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D006801:Humans; D015151:Immunoblotting; D009447:Neuroblastoma / Q000378:metabolism*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C576917:AURKA protein, human; D064096:Aurora Kinase A
AURKA; hypoxia; neuroblastoma; tumorigenesis