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ROR2 is epigenetically inactivated in the early stages of colorectal neoplasia and is associated with proliferation and migration

Overview of attention for article published in BMC Cancer, July 2016
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Title
ROR2 is epigenetically inactivated in the early stages of colorectal neoplasia and is associated with proliferation and migration
Published in
BMC Cancer, July 2016
DOI 10.1186/s12885-016-2576-7
Pubmed ID
Authors

Sean S. Q. Ma, Sameer Srivastava, Estelle Llamosas, Nicholas J. Hawkins, Luke B. Hesson, Robyn L. Ward, Caroline E. Ford

Abstract

Colorectal cancer (CRC) is closely linked to Wnt signalling, with 94 % of cases exhibiting a Wnt related mutation. ROR2 is a receptor tyrosine kinase that is thought to repress β-catenin dependent Wnt signalling. Our study aims to determine if ROR2 is epigenetically silenced in CRC and determine if in vitro silencing of ROR2 potentiates Wnt signalling, and alters the proliferative, migratory or invasive potential of cells. ROR2 expression was examined in CRC cell lines and patient adenomas using qRT-PCR, while COBRA and bisulphite sequencing was used to analyse ROR2 promoter methylation. 258 patient primary tumour samples from publicly available databases were also examined for ROR2 expression and methylation. In addition, the functional effects of ROR2 modulation were investigated in HCT116 cells following ROR2 siRNA knockdown and in RKO and SW620 cells following ectopic ROR2 expression. Reduced ROR2 expression was found to correlate with ROR2 promoter hypermethylation in colorectal cancer cell lines, carcinomas and adenomas. ROR2 expression was downregulated in 76.7 % (23/30) of CRC cell lines with increasing ROR2 promoter hypermethylation correlating with progressively lower expression. Analysis of 239 primary tumour samples from a publicly available cohort also found a significant correlation between reduced ROR2 expression and increased promoter methylation. Methylation analysis of 88 adenomas and 47 normal mucosa samples found greater percentage of adenoma samples to be methylated. Additional analysis also revealed that adenoma samples with reduced ROR2 expression also possessed ROR2 promoter hypermethylation. ROR2 knockdown in the CRC cell line HCT116 significantly decreased expression of the β-catenin independent Wnt targets genes JNK and NFATC1, increased cellular proliferation and migration but decreased invasion. When ROR2 was ectopically expressed in RKO and SW620 cells, there was no significant change to either cellular proliferation or migration. ROR2 is frequently epigenetically inactivated by promoter hypermethylation in the early stages of colorectal neoplasia and this may contribute to colorectal cancer progression by increasing cellular proliferation and migration.

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Mendeley readers

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The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 30 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 27%
Student > Master 5 17%
Researcher 5 17%
Student > Bachelor 2 7%
Lecturer 1 3%
Other 6 20%
Unknown 3 10%
Readers by discipline Count As %
Medicine and Dentistry 9 30%
Biochemistry, Genetics and Molecular Biology 8 27%
Agricultural and Biological Sciences 4 13%
Unspecified 1 3%
Veterinary Science and Veterinary Medicine 1 3%
Other 3 10%
Unknown 4 13%
Attention Score in Context

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 22 July 2016.
All research outputs
#20,336,031
of 22,881,154 outputs
Outputs from BMC Cancer
#6,506
of 8,325 outputs
Outputs of similar age
#317,800
of 363,722 outputs
Outputs of similar age from BMC Cancer
#192
of 267 outputs
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So far Altmetric has tracked 8,325 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 267 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.