PMID- 17974987
OWN - NLM
STAT- MEDLINE
DCOM- 20071127
LR  - 20220601
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 67
IP  - 21
DP  - 2007 Nov 1
TI  - Aurora-A, a negative prognostic marker, increases migration and decreases 
      radiosensitivity in cancer cells.
PG  - 10436-44
AB  - Centrosomal Aurora-A (Aur-A) kinase ensures proper spindle assembly and accurate 
      chromosome segregation in mitosis. Overexpression of Aur-A leads to centrosome 
      amplification, aberrant spindle, and consequent genetic instability. In the 
      present study, Aur-A was found to be overexpressed in laryngeal squamous cell 
      carcinoma (LSCC). Moreover, Aur-A expression was adversely correlated with median 
      survival, and further identified as a potential independent factor for disease 
      prognosis. Suppression of Aurora kinase activity chemically or genetically led to 
      LSCC Hep2 cell cycle arrest and apoptotic cell death. Importantly, we found that 
      Aur-A increases cell migration and this novel function was correlated with Akt1 
      activation. The enhanced cell migration induced by Aur-A overexpression could be 
      abrogated by either small-molecule Akt1 inhibitor or short interfering RNA. 
      VX-680, a selective Aurora kinase inhibitor, decreased Akt1 phosphorylation at 
      Ser(473) and inhibited cell migration, but failed to do so in constitutive active 
      Akt1 (myr-Akt1)-overexpressed cells. Moreover, our data suggested that 
      overexpression of Aur-A kinase might also contribute to radioresistance of LSCC. 
      Inhibiting Aur-A by VX-680 induced expression of p53 and potently sensitized 
      cells to radiotherapy, leading to significant cell death. Ectopic overexpression 
      of Aur-A, however, reduced p53 level and rendered cells more resistant to 
      irradiation. Taken together, we showed that Aur-A kinase, a negative prognostic 
      marker, promotes migration and reduces radiosensitivity in laryngeal cancer 
      cells.
FAU - Guan, Zhong
AU  - Guan Z
AD  - State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Wang, Xian-ren
AU  - Wang XR
FAU - Zhu, Xiao-feng
AU  - Zhu XF
FAU - Huang, Xue-fei
AU  - Huang XF
FAU - Xu, Jie
AU  - Xu J
FAU - Wang, Li-hui
AU  - Wang LH
FAU - Wan, Xiang-bo
AU  - Wan XB
FAU - Long, Zi-jie
AU  - Long ZJ
FAU - Liu, Jian-nan
AU  - Liu JN
FAU - Feng, Gong-kan
AU  - Feng GK
FAU - Huang, Wenlin
AU  - Huang W
FAU - Zeng, Yi-xin
AU  - Zeng YX
FAU - Chen, Fu-jin
AU  - Chen FJ
FAU - Liu, Quentin
AU  - Liu Q
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Piperazines)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 234335M86K (tozasertib)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Aurora Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Aurora Kinases
MH  - Carcinoma, Squamous Cell/*mortality/pathology/radiotherapy
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Humans
MH  - Laryngeal Neoplasms/*mortality/pathology/radiotherapy
MH  - Piperazines/pharmacology
MH  - Prognosis
MH  - Protein Serine-Threonine Kinases/analysis/antagonists & inhibitors/*physiology
MH  - Proto-Oncogene Proteins c-akt/physiology
MH  - RNA, Small Interfering/pharmacology
MH  - *Radiation Tolerance
MH  - Survival Rate
MH  - Tumor Suppressor Protein p53/physiology
EDAT- 2007/11/03 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/11/03 09:00
PHST- 2007/11/03 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/11/03 09:00 [entrez]
AID - 67/21/10436 [pii]
AID - 10.1158/0008-5472.CAN-07-1379 [doi]
PST - ppublish
SO  - Cancer Res. 2007 Nov 1;67(21):10436-44. doi: 10.1158/0008-5472.CAN-07-1379.