6790

AURKA

aurora kinase A;AURKA;aurora kinase A

ARK-1|Aurora-A kinase|IPL1-related kinase|aurora 2|aurora-related kinase 1|aurora/IPL1-like kinase|aurora/IPL1-related kinase 1|breast tumor-amplified kinase|breast-tumor-amplified kinase|hARK1|protein phosphatase 1, regulatory subunit 47|serine/threonine

20q13

protein-coding

The mitotic kinase Aurora-A (Aur-A) is required to form the bipolar spindle and ensure accurate chromosome segregation before cell division. Aur-A dysregulation represents an oncogenic event that promotes tumor formation. Here, we report that Aur-A promotes breast cancer metastasis. Aur-A overexpression enhanced mammary cell migration by dephosphorylation and activation of cofilin, which facilitates actin reorganization and polymerization. Cofilin knockdown impaired Aur-A-driven cell migration and protrusion of the cell membrane. Conversely, overexpression of activated cofilin abrogated the effects of Aur-A knockdown on cell migration. Moreover, Aur-A overexpession increased the expression of the cofilin phosphatase Slingshot-1 (SSH1), contributing to cofilin activation and cell migration. We found that phosphatidylinositol 3-kinase (PI3K) inhibition blocked Aur-A-induced cofilin dephosphorylation, actin reorganization, and cell migration, suggesting crosstalk with PI3K signaling and a potential benefit of PI3K inhibition in tumors with deregulated Aur-A. Additionally, we found an association between Aur-A overexpression and cofilin activity in breast cancer tissues. Our findings indicate that activation of the cofilin-F-actin pathway contributes to tumor cell migration and metastasis enhanced by Aur-A, revealing a novel function for mitotic Aur-A kinase in tumor progression.

PURPOSE: To investigate the expression of aurora kinase A and B in patients with chondrosarcoma and consider it as a prognostic marker and molecular target of therapy. METHODS: To evaluate the relationship of the aurora kinase A and B and the clinical pathological parameters and prognosis of chondrosarcoma. 72 case chondrosarcoma and 42 case chondroma were performed immunohistochemistry on the tissue microarray paraffin sections. The survival time of patients was followed-up. RESULTS: The expression of aurora kinase A and B in chondrosarcoma was significantly higher than that in chondroma (p<0.01). There were differences about the expression of aurora kinase A and B in chondrosarcoma between the recurrence group and the non-recurrence group, metastatic group and non-metastatic group (p<0.05), but not age and gender (p>0.05). The expression of aurora kinase A and B were significantly lower in group low grade conventional chondrosarcoma than that in groups medium and high grade conventional chondrosarcoma (p<0.01). The expression of aurora kinase A and B in chondrosarcoma showed a positive correlation (p<0.01). According to the Kaplan Meier analysis and multivariate Cox regression analysis, the survival rate was significantly different between the patients with positive aurora kinase A and the patients with negative expression (p<0.05) and aurora kinase A expression was an independent risk marker of survival (HR=11.263, 95%CI: 2.317-54.748, P=0.003). CONCLUSION: Both the aurora kinase A and B might involve in the oncogenic, invasive and metastatic process of chondrosarcoma; however, the mechanism is still unclear. The aurora kinase A and B could be used as a new prognostic marker and molecular therapeutic target for chondrosarcoma. VIRTUAL SLIDE: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9101494267377096.

The functions of Rap-1A in oral carcinogenesis are largely unexplored. In this study, we examined the expression of Rap-1A at different malignant stages of oral cavity squamous cell carcinoma (OCSCC). Semiquantitative RT-PCR, quantitative RT-PCR, and Western blotting were used to evaluate Rap-1A mRNA and protein expressions, respectively, in paired OCSCC patient specimens. To determine the possible correlation between Rap-1A expression and various clinical characteristics, 256 samples from patients with OCSCC were evaluated by immunohistochemical staining. Strong Rap-1A expression was a significant prognostic marker and predictor of aggressive OCSCC. The overall and disease-specific 5-year survival rates were significantly correlated with strong expression of Rap-1A (P < 0.001). Functionally, overexpressed Rap-1A could promote oral cancer cell migration and invasion by Transwell chambers and wound healing assay. Conversely, the suppression of Rap-1A expression using Rap-1A-mediated siRNA was sufficient to decrease cell motility. Furthermore, our data also illustrated that Aurora-A could not only induce mRNA and protein expressions of Rap-1A for enhancing cancer cell motility but also co-localize and form a complex with Rap-1A in the oral cancer cell line. Finally, immunohistochemical staining, indirect immunofluorescence, and Western blotting analysis of human aggressive OCSCC specimens revealed a significantly positive correlation between Rap-1A and Aurora-A expression. Taken together, our results suggest that the Aurora-A/Rap-1A pathway is associated with survival, tumor progression, and metastasis of OCSCC patients.

The objective of this study was to investigate the expression and clinical role of the spindle checkpoint kinase budding uninhibited by benzimidazole 1 (Bub1) in primary and metastatic advanced-stage ovarian serous carcinoma. BUB1 mRNA expression was analyzed in 178 tumors (88 effusions, 38 primary carcinomas, and 52 solid metastases) from 144 patients with advanced-stage disease using quantitative real-time polymerase chain reaction (PCR). Bub1 protein expression by Western blotting was studied in 63 carcinomas (30 effusions and 33 solid lesions). BUB1 mRNA expression at different anatomic sites was studied for association with clinicopathologic parameters, including chemotherapy resistance and survival. BUB1 mRNA was universally expressed in serous carcinomas, irrespective of anatomic site. BUB1 mRNA levels were uniformly low in six ovarian surface epithelium specimens analyzed for comparative purposes. Bub1 protein was expressed in 22/30 effusions and 28/33 solid lesions. BUB1 mRNA expression was significantly higher in chemo-naive primary carcinomas and solid metastases compared to specimens obtained following neoadjuvant chemotherapy (p < 0.001) and was unrelated to chemotherapy exposure in effusions nor to chemoresponse or survival at any anatomic site. BUB1 mRNA levels in both effusions and solid lesions were strongly related to the mRNA levels of AURKA and AURKB previously studied in this cohort (p < 0.001 for both). Bub1 is widely expressed in primary and metastatic OC, suggesting a biological role in this cancer. BUB1 mRNA levels are lower following chemotherapy exposure in solid lesions, though its presence is unrelated to clinical behavior including response to chemotherapy and survival. BUB1 is co-expressed with AURKA and AURKB suggesting biological relationship between these spindle cell components.