Aurora-A overexpression enhances cell-aggregation of Ha-rastransformants through the MEK/ERK signaling pathway

Abstract

BackgroundOverexpression of Aurora-A and mutant Ras (RasV12) together has been detected in human bladder cancer tissue. However, it is not clear whether this phenomenon is a general event or not. Although crosstalk between Aurora-A and Ras signaling pathways has been reported, the role of these two genes acting together in tumorigenesis remains unclear.MethodsReal-time PCR and sequence analysis were utilized to identify Ha- and Ki-ras mutation (Gly -> Val). Immunohistochemistry staining was used to measure the level of Aurora-A expression in bladder and colon cancer specimens. To reveal the effect of overexpression of the above two genes on cellular responses, mouse NIH3T3 fibroblast derived cell lines over-expressing either RasV12and wild-type Aurora-A (designated WT) or RasV12 and kinase-inactivated Aurora-A (KD) were established. MTT and focus formation assays were conducted to measure proliferation rate and focus formation capability of the cells. Small interfering RNA, pharmacological inhibitors and dominant negative genes were used to dissect the signaling pathways involved.ResultsOverexpression of wild-type Aurora-A and mutation of RasV12 were detected in human bladder and colon cancer tissues. Wild-type Aurora-A induces focus formation and aggregation of the RasV12 transformants. Aurora-A activates Ral A and the phosphorylation of AKT as well as enhances the phosphorylation of MEK, ERK of WT cells. Finally, the Ras/MEK/ERK signaling pathway is responsible for Aurora-A induced aggregation of the RasV12 transformants.ConclusionWild-type-Aurora-A enhances focus formation and aggregation of the RasV12 transformants and the latter occurs through modulating the Ras/MEK/ERK signaling pathway.

Overexpression of Aurora-A Enhances Invasion and Matrix Metalloproteinase-2 Expression in Esophageal Squamous Cell Carcinoma Cells

“…These results are consistent with previous finding that Aurora-A overexpression can upregulate phosphorylation level of Akt (30). However, we also found here that the Aurora-Astimulated MMP-2 secretion and expression are not mediated by ERK signaling pathway, although some reports show that Aurora-A can enhance the phosphorylation level of ERK (31). This discrepancy can be attributed to the difference in the used cancer types.…”

TACC3 promotes epithelial–mesenchymal transition (EMT) through the activation of PI3K/Akt and ERK signaling pathways

“…Recent studies indicate that overexpression of Aurora A increases Akt activation for cancer cell survival [105], and promotes the oncogenic transformation by modulating the Ras/MEK/ERK signaling pathways [106]. Moreover, Aurora A-induced EMT and the acquisition of invasive potential are mediated by MAPK phosphorylation, while the inhibition of MAPK or its upstream MEK1/2 abrogates Aurora A-mediated EMT process [107].…”

PP6 Controls T Cell Development and Homeostasis by Negatively Regulating Distal TCR Signaling

“…TAK1 is essential for the activation of JNK, p38, and NF-kB in T cells (23). Aurora A has been shown to activate AKT (38,39) and ERK (38)(39)(40)(41) in cancer cell lines. TAK1 phosphorylation was markedly reduced in PP6-deficient thymocytes after PMA/ ionomycin stimulation (Fig.…”