Evidence map›Paper›PMID 27340238›Full record

ArticleMolecular & cellular proteomics : MCP2016

Oncogenic KRAS and BRAF Drive Metabolic Reprogramming in Colorectal Cancer.

Josiah E Hutton, Xiaojing Wang, Lisa J Zimmerman, Robbert J C Slebos, Irina A Trenary, Jamey D Young, Ming Li, Daniel C Liebler

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% 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

83 citing papers in PubMed, 1 synthesis or guideline pooled it, 143 citations in OpenAlex.

  1. Pooled it
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  9. Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026
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23 more citing papers are in PubMed but not listed here.

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

8 authors at 1 institution in 1 country.

Josiah E HuttonFrom the ‡Department of Biochemistry.
Xiaojing Wang§Department of Biomedical Informatics.
Lisa J ZimmermanFrom the ‡Department of Biochemistry, ¶Jim Ayers Institute for Precancer Detection and Diagnosis.
Robbert J C SlebosFrom the ‡Department of Biochemistry, ¶Jim Ayers Institute for Precancer Detection and Diagnosis.
Irina A Trenary‖Chemical & Biomolecular Engineering.
Jamey D Young‖Chemical & Biomolecular Engineering, **Molecular Physiology & Biophysics.
Ming Li‡‡Department of Biostatistics, Vanderbilt University, Nashville, Tennessee 37232.
Daniel C LieblerFrom the ‡Department of Biochemistry, ¶Jim Ayers Institute for Precancer Detection and Diagnosis, daniel.liebler@vanderbilt.edu.
Vanderbilt University · US

Funding

Vanderbilt Proteome Characterization CenterU24CA159988 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LIEBLER, DANIEL C · 2011 to 2016
$13.9M
NCI NIH HHS U24 CA159988
6 · The paper itself

Abstract

Metabolic reprogramming, in which altered utilization of glucose and glutamine supports rapid growth, is a hallmark of most cancers. Mutations in the oncogenes KRAS and BRAF drive metabolic reprogramming through enhanced glucose uptake, but the broader impact of these mutations on pathways of carbon metabolism is unknown. Global shotgun proteomic analysis of isogenic DLD-1 and RKO colon cancer cell lines expressing mutant and wild type KRAS or BRAF, respectively, failed to identify significant differences (at least 2-fold) in metabolic protein abundance. However, a multiplexed parallel reaction monitoring (PRM) strategy targeting 73 metabolic proteins identified significant protein abundance increases of 1.25-twofold in glycolysis, the nonoxidative pentose phosphate pathway, glutamine metabolism, and the phosphoserine biosynthetic pathway in cells with KRAS G13D mutations or BRAF V600E mutations. These alterations corresponded to mutant KRAS and BRAF-dependent increases in glucose uptake and lactate production. Metabolic reprogramming and glucose conversion to lactate in RKO cells were proportional to levels of BRAF V600E protein. In DLD-1 cells, these effects were independent of the ratio of KRAS G13D to KRAS wild type protein. A study of 8 KRAS wild type and 8 KRAS mutant human colon tumors confirmed the association of increased expression of glycolytic and glutamine metabolic proteins with KRAS mutant status. Metabolic reprogramming is driven largely by modest (<2-fold) alterations in protein expression, which are not readily detected by the global profiling methods most commonly employed in proteomic studies. The results indicate the superiority of more precise, multiplexed, pathway-targeted analyses to study functional proteome systems. Data are available through MassIVE Accession MSV000079486 at ftp://MSV000079486@massive.ucsd.edu.

Indexed as

Biosynthetic PathwaysCell Line, TumorColorectal NeoplasmsGene Expression Regulation, NeoplasticGlucoseHumansLactic AcidMutationProteomicsProto-Oncogene Proteins B-rafras ProteinsBRAF protein, humanGlucoseLactic AcidProto-Oncogene Proteins B-rafras Proteins

Identifiers

PMID27340238
PMCPMC5013308
OpenAlexW2467465063

What OpenQuestion holds

Textmetadata
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.