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Linking FOXO3, NCOA3, and TCF7L2 to Ras pathway phenotypes through a genome-wide forward genetic screen in human colorectal cancer cells

Overview of attention for article published in Genome Medicine, January 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (88th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (61st percentile)

Mentioned by

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19 tweeters
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1 Google+ user

Readers on

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17 Mendeley
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Title
Linking FOXO3, NCOA3, and TCF7L2 to Ras pathway phenotypes through a genome-wide forward genetic screen in human colorectal cancer cells
Published in
Genome Medicine, January 2018
DOI 10.1186/s13073-017-0511-4
Pubmed ID
Authors

Snehangshu Kundu, Muhammad Akhtar Ali, Niklas Handin, Narendra Padhan, Jimmy Larsson, Maria Karoutsou, Kenneth Ban, Jacek R. Wiśniewski, Per Artursson, Liqun He, Mats Hellström, Tobias Sjöblom

Abstract

The Ras pathway genes KRAS, BRAF, or ERBBs have somatic mutations in ~ 60% of human colorectal carcinomas. At present, it is unknown whether the remaining cases lack mutations activating the Ras pathway or whether they have acquired mutations in genes hitherto unknown to belong to the pathway. To address the second possibility and extend the compendium of Ras pathway genes, we used genome-wide transposon mutagenesis of two human colorectal cancer cell systems deprived of their activating KRAS or BRAF allele to identify genes enabling growth in low glucose, a Ras pathway phenotype, when targeted. Of the 163 recurrently targeted genes in the two different genetic backgrounds, one-third were known cancer genes and one-fifth had links to the EGFR/Ras/MAPK pathway. When compared to cancer genome sequencing datasets, nine genes also mutated in human colorectal cancers were identified. Among these, stable knockdown of FOXO3, NCOA3, and TCF7L2 restored growth in low glucose but reduced MEK/MAPK phosphorylation, reduced anchorage-independent growth, and modulated expressions of GLUT1 and Ras pathway related proteins. Knockdown of NCOA3 and FOXO3 significantly decreased the sensitivity to cetuximab of KRAS mutant but not wild-type cells. This work establishes a proof-of-concept that human cell-based genome-wide forward genetic screens can assign genes to pathways with clinical importance in human colorectal cancer.

Twitter Demographics

The data shown below were collected from the profiles of 19 tweeters 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 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 35%
Researcher 4 24%
Student > Master 2 12%
Student > Doctoral Student 2 12%
Student > Bachelor 1 6%
Other 1 6%
Unknown 1 6%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 47%
Agricultural and Biological Sciences 3 18%
Medicine and Dentistry 3 18%
Neuroscience 1 6%
Unknown 2 12%

Attention Score in Context

This research output has an Altmetric Attention Score of 17. 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 15 April 2018.
All research outputs
#1,100,904
of 14,805,703 outputs
Outputs from Genome Medicine
#263
of 1,030 outputs
Outputs of similar age
#44,586
of 399,774 outputs
Outputs of similar age from Genome Medicine
#31
of 81 outputs
Altmetric has tracked 14,805,703 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,030 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.8. This one has gotten more attention than average, scoring higher than 74% of its peers.
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 399,774 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 88% of its contemporaries.
We're also able to compare this research output to 81 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 61% of its contemporaries.