Targeting aurora kinase A inhibits hypoxia-mediated neuroblastoma cell tumorigenesis.

Abstract:

BACKGROUND/AIM: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. MATERIALS AND 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. CONCLUSION: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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Romain CV,Paul P,Lee S,Qiao J,Chung DH

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

2269-74

issue

5

eissn

0250-7005

issn

1791-7530

pii

34/5/2269

journal_volume

34

pub_type

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