Cancer

Laryngeal carcinomas; Laryngeal squamous cell carcinomas; Breast cancer; Colorectal cancer; neuroblastomas; Colon cancer; Atypical teratoid rhabdoid tumours; neuroblastomas, susceptibility

AurA appears to be a tumour requiring protein (TRP). The active form of the protein kinase normally acts to promote tumour cell proliferation. Although AurA is not an oncoprotein, it required for upstream oncoproteins to promote tumour formation. its low rate of mutation and down-regulation in human cancers supports it identification as a tumour-requiring protein, and as a target for cancer drug development.
 

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Barrett's esophagus epithelial metaplasia (%CFC= +366, p<0.005); Breast non-basal-like cancer (BLC) (%CFC= +65, p<0.0001); Breast sporadic basal-like cancer (BLC) (%CFC= +81, p<0.0001); Cervical cancer (%CFC= -76, p<0.0001); Classical Hodgkin lymphomas (%CFC= +157, p<0.0001); Colon mucosal cell adenomas (%CFC= +121, p<0.0001); Head and neck squamous cell carcinomas (HNSCC) (%CFC= +47, p<0.003); Large B-cell lymphomas (%CFC= +224, p<0.0001); Lung adenocarcinomas (%CFC= +237, p<0.0001); Oral squamous cell carcinomas (OSCC) (%CFC= +246, p<0.0001); Ovary adenocarcinomas (%CFC= +935, p<0.005); Prostate cancer - metastatic (%CFC= +90, p<0.0001); Prostate cancer - primary (%CFC= +87, p<0.039); Skin fibrosarcomas (%CFC= +471, p<0.0008); Skin melanomas - malignant (%CFC= +143, p<0.0001); Skin squamous cell carcinomas (%CFC= +183, p<0.008); and Vulvar intraepithelial neoplasia (%CFC= +411, p<0.0002). The COSMIC website notes an up-regulated expression score for AurA in diverse human cancers of 1011, which is 2.2-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 6 for this protein kinase in human cancers was 0.1-fold of the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis. AurA phosphotransferase activity can be abrogated with a K162R mutation, decreased 10-fold with G198N (which also induces abnormal binding to INCENP and BIRC5), and increased with T288D. Phosphatase type I interactions can be decreased with F165A, and F346A mutations, while ubiquitination can be reduced with R205A. Autophosphorylation can be inhibited with D274N, and TPX2 interactions can be interrupted with a T287E mutation.

Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 25634 diverse cancer specimens. This rate is very similar (+ 3% higher) to the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 0.54 % in 1184 large intestine cancers tested; 0.34 % in 805 skin cancers tested.

None > 5 in 20,852 cancer specimens

Only 1 deletion, no insertions and no complex mutations are noted on the COSMIC website.