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 hypoxiainduced 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 hypoxiamediated tumor progression in neuroblastoma.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2269-2274 |
| Number of pages | 6 |
| Journal | Anticancer Research |
| Volume | 34 |
| Issue number | 5 |
| State | Published - May 1 2014 |
| Externally published | Yes |
Keywords
- AURKA
- Hypoxia
- Neuroblastoma
- Tumorigenesis
ASJC Scopus subject areas
- Oncology
- Cancer Research