Evidence map›Paper›PMID 34822010›Full record

ArticleMetabolomics : Official journal of the Metabolomic Society2021

Metabonomics study of the effects of single copy mutant KRAS in the presence or absence of WT allele using human HCT116 isogenic cell lines.

Dorna Varshavi, Dorsa Varshavi, Nicola McCarthy, Kirill Veselkov, Hector C Keun, Jeremy R Everett

Open access · hybridAbstract read
In one paragraph

Article in Metabolomics : Official journal of the Metabolomic Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.2field-weighted citation impact, top 50% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 5 institutions in 2 countries.

Dorna VarshaviMedway Metabonomics Research Group, University of Greenwich, Chatham Maritime, ME4 4TB, Kent, UK.
Dorsa VarshaviMedway Metabonomics Research Group, University of Greenwich, Chatham Maritime, ME4 4TB, Kent, UK.
Nicola McCarthyHorizon Discovery Ltd., Cambridge Research Park, 8100 Beach Dr, Waterbeach, Cambridge, CB25 9TL, UK.
Kirill VeselkovDepartment of Surgery and Cancer, Faculty of Medicine, Imperial College, London, SW7 2AZ, UK.
Hector C KeunDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, W12 ONN, UK.
Jeremy R EverettMedway Metabonomics Research Group, University of Greenwich, Chatham Maritime, ME4 4TB, Kent, UK. j.r.everett@greenwich.ac.uk.ORCID 0000-0003-1550-4482
University of Alberta · CAHammersmith Hospital · GBHorizon Discovery (United Kingdom) · GBImperial College London · GBUniversity of Greenwich · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionKRAS was one of the earliest human oncogenes to be described and is one of the most commonly mutated genes in different human cancers, including colorectal cancer. Despite KRAS mutants being known driver mutations, KRAS has proved difficult to target therapeutically, necessitating a comprehensive understanding of the molecular mechanisms underlying KRAS-driven cellular transformation.

objectivesTo investigate the metabolic signatures associated with single copy mutant KRAS in isogenic human colorectal cancer cells and to determine what metabolic pathways are affected.

methodsUsing NMR-based metabonomics, we compared wildtype (WT)-KRAS and mutant KRAS effects on cancer cell metabolism using metabolic profiling of the parental KRAS

resultsMutation in the KRAS oncogene leads to a general metabolic remodelling to sustain growth and counter stress, including alterations in the metabolism of amino acids and enhanced glutathione biosynthesis. Additionally, we show that KRAS

conclusionsOur study showed the effect of a single point mutation in one KRAS allele and KRAS allele loss in an isogenic genetic background, hence avoiding confounding genetic factors. Metabolic differences among different KRAS mutations might play a role in their different responses to anticancer treatments and hence could be exploited as novel metabolic vulnerabilities to develop more effective therapies against oncogenic KRAS.

Indexed as

Colorectal NeoplasmsProto-Oncogene Proteins p21(ras)AllelesCell LineHumansMetabolomicsKRAS protein, humanProto-Oncogene Proteins p21(ras)CellsColorectal cancerHCT116KRASMetabolic profilingMetabolomicsMetabonomicsMutationsNMR

Identifiers

PMID34822010
PMCPMC8616861
OpenAlexW3217218173

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.