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Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer

Overview of attention for article published in Molecular Cancer, April 2015
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2 X users
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1 peer review site

Citations

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15 Dimensions

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17 Mendeley
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Title
Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer
Published in
Molecular Cancer, April 2015
DOI 10.1186/s12943-015-0348-7
Pubmed ID
Authors

Chang-Han Chen, Alice YW Chang, Shau-Hsuan Li, Hsin-Ting Tsai, Li-Yen Shiu, Li-Jen Su, Wen-Lung Wang, Tai-Jen Chiu, Sheng-Dean Luo, Tai-Lin Huang, Chih-Yen Chien

Abstract

Head and neck cancer (HNC) is a highly invasive cancer. Aurora-A has been reported for a number of malignancies. However, the identity of downstream effectors responsible for its aggressive phenotype in HNC remains underinvestigated. The mRNA and protein expression levels of Aurora-A and FLJ10540 were assessed in HNC specimens and cell lines using RT-qPCR, western blot, Oncomine, and microarray database analysis. The downstream molecular mechanisms of Aurora-A were confirmed by RT-qPCR, western blot, luciferase reporter, confocal microscopy analyses, immunoprecipitation, colony formation, cell viability, and xenograft model. Cellular functions in response to Aurora-A-modulated downstream targets such as FLJ10540 and MMPs were examined in vitro and in vivo, including cell growth, motility and chemosensitivity. Aurora-A/FLJ10540/MMPs expression was determined in cancer and adjacent normal tissues from HNC patients by immunohistochemistry approach. In the current study, Aurora-A exhibited similar gene expression profiles with FLJ10540 by using accessibly public microarray and Oncomine database analysis, raising the possibility that these molecules might coordinately participate in cancer progression and metastasis of HNC. These two molecules connection were also examined in cell lines and tissues of HNC. Aurora-A overexpression could not only bind to the promoter of FLJ10540 to induce FLJ10540 expression, but also increase both mRNA and protein levels of MMP-7 and MMP-10 in HNC cells. Conversely, depletion of Aurora-A expression by using siRNA or Aurora-A kinase inhibitor, MLN8237, suppressed FLJ10540, MMP-7 and MMP-10 mRNA and protein expressions in vitro and in vivo. In addition, the FLJ10540-PI3K complex was destroyed by inhibition the Aurora-A kinase activity. Forced overexpression of FLJ10540 in Aurora-A-depleted or in MLN8237-treated HNC cells attenuated the effect on cytotoxicity to cisplatin. Elevated Aurora-A expression in HNC cells led to the characteristics of more aggressive malignancy, including enhanced chemoresistance and increased the abilities of proliferation, migration and invasion, which was required for FLJ10540/MMP-7 or FLJ10540/MMP-10 expressions. Finally, immunohistochemical analysis of human HNC specimens showed a significant positively correlation among Aurora-A, FLJ10540, MMP-7 and MMP-10 expressions. Together, our findings define a novel mechanism by which Aurora-A promotes cell malignancy, with potential implications for understanding the clinical action of Aurora-A.

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
India 1 6%
Unknown 16 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 24%
Researcher 3 18%
Other 2 12%
Student > Bachelor 2 12%
Lecturer 1 6%
Other 3 18%
Unknown 2 12%
Readers by discipline Count As %
Medicine and Dentistry 7 41%
Agricultural and Biological Sciences 3 18%
Psychology 1 6%
Biochemistry, Genetics and Molecular Biology 1 6%
Physics and Astronomy 1 6%
Other 1 6%
Unknown 3 18%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 December 2016.
All research outputs
#14,221,392
of 22,799,071 outputs
Outputs from Molecular Cancer
#902
of 1,720 outputs
Outputs of similar age
#139,459
of 264,665 outputs
Outputs of similar age from Molecular Cancer
#20
of 46 outputs
Altmetric has tracked 22,799,071 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,720 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 43rd percentile – i.e., 43% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 264,665 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 46 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.