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FoxM1 transactivates PTTG1 and promotes colorectal cancer cell migration and invasion

Overview of attention for article published in BMC Medical Genomics, August 2015
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Title
FoxM1 transactivates PTTG1 and promotes colorectal cancer cell migration and invasion
Published in
BMC Medical Genomics, August 2015
DOI 10.1186/s12920-015-0126-9
Pubmed ID
Authors

Yun Zheng, Jinjun Guo, Jin Zhou, Jinjian Lu, Qi Chen, Cui Zhang, Chen Qing, H. Philip Koeffler, Yunguang Tong

Abstract

Metastasis is the major cause of cancer-related death. Forkhead Box M1 (FoxM1) is a master regulator of tumor metastasis. This study aims to identify new FoxM1 targets in regulating tumor metastasis using bioinformatics tools as well as biological experiments. Illumina microarray was used to profile WT and PTTG1 knockout HCT116 cells. R2 Genomics Analysis was used to identify PTTG1 as a potential FoxM1 targeted gene. Luciferase reporter array, EMSA and Chromatin Immunoprecipitation (ChIP) were used to determine the binding of FoxM1 to PTTG1 promoter. Boyden chamber assay was used to evaluate the effects of FoxM1-PTTG1 on cell migration and invasion. Splenic-injection induced liver metastasis model was used to evaluate the effects of FoxM1-PTTG1 on liver metastasis of colorectal cancer. Analyses of multiple microarray datasets derived from human colorectal cancer indicated that correlation levels of FoxM1 and pituitary tumor transforming gene (PTTG1) are highly concordant (R = 0.68 ~ 0.89, p = 2.1E-226 ~ 9.6E-86). FoxM1 over-expression increased and knock-down decreased PTTG1 expression. Luciferase reporter assay identified that the -600 to -300 bp region of PTTG1 promoter is important for FoxM1 to enhance PTTG1 promoter activity. EMSA and ChIP assays confirmed that FoxM1 directly binds to PTTG1 promoter at the -391 to -385 bp region in colorectal cancer cells. Boyden chamber assay indicated that both FoxM1 and PTTG1 regulate migration and invasion of HCT116 and SW620 colorectal cancer cells. Further in vivo assays indicated that PTTG1 knock out decreased the liver metastasis of FoxM1 over-expressing HCT116 cells. Microarray analyses identified 662 genes (FDR < 0.05) differentially expressed between WT and PTTG1(-/-) HCT116 cells. Among them, dickkopf homolog 1 (DKK1), a known WNT pathway inhibitor, was suppressed by PTTG1 and FoxM1. PTTG1 is a FoxM1 targeted gene. FoxM1 binds to PTTG1 promoter to enhance PTTG1 transcription, and FoxM1-PTTG1 pathway promotes colorectal cancer migration and invasion.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 23%
Student > Bachelor 6 15%
Student > Master 6 15%
Researcher 4 10%
Student > Postgraduate 3 8%
Other 3 8%
Unknown 8 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 26%
Agricultural and Biological Sciences 8 21%
Medicine and Dentistry 8 21%
Immunology and Microbiology 1 3%
Unknown 12 31%
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 28 August 2015.
All research outputs
#14,821,227
of 22,821,814 outputs
Outputs from BMC Medical Genomics
#606
of 1,223 outputs
Outputs of similar age
#145,819
of 264,494 outputs
Outputs of similar age from BMC Medical Genomics
#15
of 18 outputs
Altmetric has tracked 22,821,814 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,223 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 44th percentile – i.e., 44% 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 264,494 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 18 others from the same source and published within six weeks on either side of this one. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.