↓ Skip to main content

NPC1L1 knockout protects against colitis-associated tumorigenesis in mice

Overview of attention for article published in BMC Cancer, March 2015
Altmetric Badge

Mentioned by

twitter
1 tweeter

Citations

dimensions_citation
23 Dimensions

Readers on

mendeley
22 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
NPC1L1 knockout protects against colitis-associated tumorigenesis in mice
Published in
BMC Cancer, March 2015
DOI 10.1186/s12885-015-1230-0
Pubmed ID
Authors

Jianming He, Hyunsu Shin, Xing Wei, Anil Kumar G Kadegowda, Rui Chen, Sandy Krystal Xie

Abstract

Colorectal cancer is strongly associated with lipid metabolism. NPC1L1, a sterol transporter, plays a key role in modulating lipid homeostasis in vivo. Its inhibitor, ezetimibe, began to be used clinically to lower cholesterol and this caused the great debate on its role in causing carcinogenesis. Here we explored the role of NPC1L1 in colorectal tumorigenesis. Wild-type mice and NPC1L1(-/-) (NPC1L1 knockout) mice were treated with azoxymethane (AOM)-dextran sodium sulfate (DSS) to induce colitis-associated colorectal tumorigenesis. Mice were sacrificed 10, 15, 18 or 20 weeks after AOM treatment, respectively. Colorectal tumors were counted and analyzed. Plasma lipid concentrations were measured using enzymatic reagent kit. Protein expression level was assayed by western blot. NPC1L1(-/-) mice significantly had fewer tumors than wild-type. The ratio of malignant/tumor in NPC1L1(-/-) mice was significantly lower than in wild-type 20 weeks after AOM-DSS treatment. NPC1L1 was highly expressed in the small intestine of wild-type mice but its expression was undetectable in colorectal mucous membranes or tumors in either group. NPC1L1 knockout decreased plasma total cholesterol and phospholipid. NPC1L1(-/-) mice had significant lower intestinal inflammation scores and expressed inflammatory markers p-c-Jun, p-ERK and Caspase-1 p20 lower than wild-type. NPC1L1 knockout also reduced lymphadenectasis what may be caused by inflammation. NPC1L1 knockout in mice decreased β-catenin in tumors and regulated TGF-β and p-gp in adjacent colons or tumors. There was not detectable change of p53 by NPC1L1 knockout. Our results provide the first evidence that NPC1L1 knockout protects against colitis-associated tumorigenesis. NPC1L1 knockout decreasing plasma lipid, especially cholesterol, to reduce inflammation and decreasing β-catenin, p-c-Jun and p-ERK may be involved in the mechanism.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 5%
Unknown 21 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 18%
Student > Bachelor 4 18%
Researcher 3 14%
Student > Doctoral Student 2 9%
Lecturer 1 5%
Other 2 9%
Unknown 6 27%
Readers by discipline Count As %
Medicine and Dentistry 5 23%
Biochemistry, Genetics and Molecular Biology 4 18%
Agricultural and Biological Sciences 3 14%
Immunology and Microbiology 2 9%
Unspecified 1 5%
Other 0 0%
Unknown 7 32%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 02 January 2016.
All research outputs
#12,395,776
of 14,011,199 outputs
Outputs from BMC Cancer
#4,297
of 5,349 outputs
Outputs of similar age
#192,772
of 233,395 outputs
Outputs of similar age from BMC Cancer
#1
of 1 outputs
Altmetric has tracked 14,011,199 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,349 research outputs from this source. They receive a mean Attention Score of 4.0. This one is in the 1st percentile – i.e., 1% 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 233,395 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them