Dataset Information

Aurora-A down-regulates IkappaBalpha via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival.

ABSTRACT:

Background

The mitotic Aurora-A kinase exerts crucial functions in maintaining mitotic fidelity. As a bona fide oncoprotein, Aurora-A aberrant overexpression leads to oncogenic transformation. Yet, the mechanisms by which Aurora-A enhances cancer cell survival remain to be elucidated.

Results

Here, we found that Aurora-A overexpression was closely correlated with clinic stage and lymph node metastasis in tongue carcinoma. Aurora-A inhibitory VX-680 suppressed proliferation, induced apoptosis and markedly reduced migration in cancer cells. We further showed that insulin-like growth factor-1, a PI3K physiological activator, reversed VX-680-decreased cell survival and motility. Conversely, wortmannin, a PI3K inhibitor, combined with VX-680 showed a synergistic effect on inducing apoptosis and suppressing migration. In addition, Aurora-A inhibition suppressed Akt activation, and VX-680-induced apoptosis was attenuated by Myr-Akt overexpression, revealing a cross-talk between Aurora-A and PI3K pathway interacting at Akt activation. Significantly, we showed that suppression of Aurora-A decreased phosphorylated Akt and was associated with increased IkappaBalpha expression. By contrast, Aurora-A overexpression upregulated Akt activity and downregulated IkappaBalpha, these changes were accompanied by nuclear translocation of nuclear factor-kappaB and increased expression of its target gene Bcl-xL. Lastly, Aurora-A overexpression induced IkappaBalpha reduction was abrogated by suppression of Akt either chemically or genetically.

Conclusion

Taken together, our data established that Aurora-A, via activating Akt, stimulated nuclear factor-kappaB signaling pathway to promote cancer cell survival, and promised a novel combined chemotherapy targeting both Aurora-A and PI3K in cancer treatment.

SUBMITTER: Yao JE

PROVIDER: S-EPMC2780390 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Aurora-A down-regulates IkappaBalpha via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival.

Yao Jin-E JE Yan Min M Guan Zhong Z Pan Chao-Bin CB Xia Liang-Ping LP Li Chuan-Xing CX Wang Li-Hui LH Long Zi-Jie ZJ Zhao Yan Y Li Ming-Wei MW Zheng Fei-Meng FM Xu Jie J Lin Dong-Jun DJ Liu Quentin Q

Molecular cancer 20091105

<h4>Background</h4>The mitotic Aurora-A kinase exerts crucial functions in maintaining mitotic fidelity. As a bona fide oncoprotein, Aurora-A aberrant overexpression leads to oncogenic transformation. Yet, the mechanisms by which Aurora-A enhances cancer cell survival remain to be elucidated.<h4>Results</h4>Here, we found that Aurora-A overexpression was closely correlated with clinic stage and lymph node metastasis in tongue carcinoma. Aurora-A inhibitory VX-680 suppressed proliferation, induce ...[more]

PMID: 19891769

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Dataset Information

Aurora-A down-regulates IkappaBalpha via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival.

Background

Results

Conclusion

Publications

Aurora-A down-regulates IkappaBalpha via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival.

Similar Datasets

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