Aurora Kinases: New Targets for Cancer Therapy

Carvajal, Richard D.; Tse, Archie; Schwartz, Gary K.

doi:10.1158/1078-0432.ccr-06-1405

Cited by 250 publications

(205 citation statements)

References 47 publications

Supporting

Mentioning

199

Contrasting

Unclassified

Order By: Relevance

“…Human Aurora-A is commonly amplified in epithelial malignant tumors, and more than 50% of ovarian and breast cancers show enhanced activation of this kinase (13,14). It has been shown that rodent fibroblasts transfected with Aurora-A form tumors in nude mice, indicating that Aurora-A is a cancer susceptibility gene (15).…”

Section: Introductionmentioning

confidence: 99%

SPINDLIN1 Promotes Cancer Cell Proliferation through Activation of WNT/TCF-4 Signaling

Wang¹,

Zeng²,

Chen³

et al. 2012

Molecular Cancer Research

View full text Add to dashboard Cite

SPINDLIN1, a new member of the SPIN/SSTY gene family, was first identified as a gene highly expressed in ovarian cancer cells. We have previously shown that it is involved in the process of spindle organization and chromosomal stability and plays a role in the development of cancer. Nevertheless, the mechanisms underlying its oncogenic role are still largely unknown. Here, we first showed that expression of SPINDLIN1 is upregulated in clinical tumors. Ectopic expression of SPINDLIN1 promoted cancer cell proliferation and activated WNT/T-cell factor (TCF)-4 signaling. The Ser84 and Ser99 amino acids within SPINDLIN1 were further identified as the key functional sites in WNT/TCF-4 signaling activation. Mutation of these two sites of SPINDLIN1 abolished its effects on promoting WNT/TCF-4 signaling and cancer cell proliferation. We further found that Aurora-A could interact with and phosphorylate SPINDLIN1 at its key functional sites, Ser84 and Ser99, suggesting that phosphorylation of SPINDLIN1 is involved in its oncogenic function. Collectively, these results suggest that SPINDLIN1, which may be a novel substrate of the Aurora-A kinase, promotes cancer cell growth through WNT/ TCF-4 signaling activation. Mol Cancer Res; 10(3); 326-35. Ó2012 AACR.

show abstract

Section: Introductionmentioning

confidence: 99%

SPINDLIN1 Promotes Cancer Cell Proliferation through Activation of WNT/TCF-4 Signaling

Wang¹,

Zeng²,

Chen³

et al. 2012

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…2 Recent evidence suggests a group of serine-threonine kinases, known as Aurora kinases, to have an important role in carcinogenesis as key regulators of mammalian mitosis, crucial for identical and exact segregation of genomic material during cell division. 3 It is proposed that aberrations of chromosome segregation potentially causes aneuploidy and is therefore triggering carcinogenesis. 4 Thus, it is not unexpected that these kinases have been described to be related with chromosomal instability, agressive growth and poor outcome in leukemia and in various malignancies like breast, bladder, ovarian, pancreatic and colon cancer.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 AURKB is found on chromosome 17p13, an area not typically amplified by tumors. 3 Beside the lack of amplification on gene level, several studies revealed an overexpression of mRNA and protein levels in several malignancies, associated with lymph node invasion, proliferation and metastasis. [14][15][16][17][18] AURKB belongs to the family of chromosomal passenger proteins and is essential for accurate chromosomal segregation and orientation, spindle assembly checkpoint, chromosome condensation, nuclear envelope formation and cytokinesis.…”

Section: Introductionmentioning

confidence: 99%

“…[14][15][16][17][18] AURKB belongs to the family of chromosomal passenger proteins and is essential for accurate chromosomal segregation and orientation, spindle assembly checkpoint, chromosome condensation, nuclear envelope formation and cytokinesis. 3,19,20 There is not much information available regarding polymorphisms in both genes. A single-nucleotide polymorphism in AURKA, AURKA Phe31Ile, has been described as a candidate low-penetrance tumor-susceptibility gene in breast-, prostate-, ovarian-, lung-, esophageal-, nonmelanoma skin-and colon cancer.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer

Pohl

Azuma²,

Zhang

et al. 2010

Pharmacogenomics J

View full text Add to dashboard Cite

Aurora kinases are conserved eukaryotic serine-threonine kinases, which serve as key regulators of mammalian mitosis. Several studies revealed a distinct correlation between inaccurate chromosome segregation, leading to chromosomal number instability, cancer progression and poor outcome. The aim of this study was to investigate the correlation of Aurora kinases A (AURKA) and B (AURKB) with overall survival (OS) by quantifying gene expression analysis and evaluation of single-nucleotide polymorphisms (SNPs) in human colorectal cancer samples and assessing the associations with clinicopathological features. We evaluated intratumoral gene expression levels and SNPs of AURKA and -B from 41 patients with metastatic colorectal cancer (mCRC). Patients with a high expression level of AURKB (41.28) lived significantly shorter (n ¼ 11, median OS ¼ 6.4 months, 95% confidence interval (CI): 3.0-14.5 months) compared with patients with a low expression level (p1.28) (n ¼ 30, median OS ¼ 18.4 months, 95% CI: 14.7-27.8 months, P ¼ 0.026, Wald's test). Patients harboring any G-allele in AURKB 885A4G showed a significantly decreased OS (P ¼ 0.05, log-rank test). We did not find any associations with clinicopathological variables and AURKA gene expression levels. Our results suggest a potential role for AURKB inhibition in patients with mCRC; thereby supporting its potential role as a target in mCRC.

show abstract

“…AURKA is highly expressed relative to normal tissue and amplified in multiple human tumors (Zhou et al, 1998). Amplification of the AURKA gene has been taken as evidence that the kinase activity of AURKA is under selective pressure during tumorigenesis, and, as a consequence, inhibitors of AURKA kinase are being developed as anticancer therapeutics (Carvajal et al, 2006). In addition to neuroblastoma both MYCN and AURKA are expressed at high levels in glioblastoma, astrocytoma, and prostate carcinoma, suggesting that stabilization of MYCN by AURKA may not be restricted to childhood tumors.…”

Section: Discussionmentioning

confidence: 99%

Chromosome Imbalances and Alterations of AURKA and MYCN Genes in Children with Neuroblastoma

Yılmaz¹,

Demırhan²,

Erdoğan³

et al. 2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: Neuroblastoma (NB), like most human cancers, is characterized by genomic instability, manifested at the chromosomal level as allelic gain, loss or rearrangement. Genetics methods, as well as conventional and molecular cytogenetics may provide valuable clues for the identification of target loci and successful search for major genes in neuroblastoma. We aimed to investigate AURKA and MYCN gene rearrangements and the chromosomal aberrations (CAs) to determine the prognosis of neuroblastoma. Methods: We performed cytogenetic analysis by G-banding in 25 cases [11 girls (44%) and 14 boys (66%)] and in 25 controls. Fluorescence in situ hybridization (FISH) with AURKA and MYCN gene probes was also used on interphase nuclei to screen for alterations. Results: Some 18.4% of patient cells exhibited CAs., with a significant difference between patient and control groups in the frequencies (P<0.0001). Some 72% of the cells had structural aberrations, and only 28% had numerical chnages in patients. Structural aberrations consisted of deletions, translocations, breaks and fragility in various chromosomes, 84% and 52% of the patients having deletions and translocations, respectively. Among these expressed CAs, there was a higher frequency at 1q21, 1q32, 2q21, 2q31, 2p24, 4q31, 9q11, 9q22, 13q14, 14q11.2, 14q24, and

show abstract

Aurora Kinases: New Targets for Cancer Therapy

Abstract: The Aurora kinase family is a collection of highly related serine/threonine kinases that functions as

Cited by 250 publications

References 47 publications

SPINDLIN1 Promotes Cancer Cell Proliferation through Activation of WNT/TCF-4 Signaling

SPINDLIN1 Promotes Cancer Cell Proliferation through Activation of WNT/TCF-4 Signaling

Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer

Chromosome Imbalances and Alterations of AURKA and MYCN Genes in Children with Neuroblastoma

Contact Info

Product

Resources

About