Evidence map›Paper›PMID 41781387›Full record

ArticleNPJ systems biology and applications2026

Cancer-associated fibroblasts drive metabolic heterogeneity in colorectal cancer cells: predictions from metabolic modeling.

Elizabeth Elton, Niki Tavakoli, Handan Cetin, Stacey D Finley

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ systems biology and applications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

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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

1 citing paper in PubMed.

  1. Review
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

4 authors.

Elizabeth EltonAlfred E. Mann Department of Biomedical Engineering, University of Southern, California, Los Angeles, California, CA, USA.
Niki TavakoliAlfred E. Mann Department of Biomedical Engineering, University of Southern, California, Los Angeles, California, CA, USA.
Handan CetinDepartment of Quantitative and Computational Biology, University of Southern, California, Los Angeles, California, CA, USA.
Stacey D FinleyAlfred E. Mann Department of Biomedical Engineering, University of Southern, California, Los Angeles, California, CA, USA. sfinley@usc.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

KRAS-mutant colorectal cancer (CRC) undergoes metabolic reprogramming that promotes tumor progression and drug resistance. Cancer-associated fibroblasts (CAFs), a major component of the tumor microenvironment (TME), play a pivotal role in modulating these metabolic adaptations in CRC. This study applies flux sampling combined with representation learning and hierarchical clustering to a computational model of central carbon metabolism to understand how CAFs influence KRAS-mutant CRC metabolic reprogramming following targeted enzyme knockdowns. Focusing on 12 key enzymes involved in glycolysis and the pentose phosphate pathway, knockdowns were simulated under normal CRC media and CAF-conditioned media (CCM) conditions. Analysis revealed CCM induces greater metabolic heterogeneity, with knockdown models exhibiting more variable and distinct metabolic states compared to those cultured in normal CRC media, indicating CAF-derived factors diversify the metabolic responses of CRC cells to enzyme perturbations. Pathway-level flux analysis demonstrated media-specific shifts in central carbon metabolism. Predicted biomass flux showed enzyme knockdowns reduced growth across both conditions, but CCM models indicated a protective effect against perturbation. Overall, simulations illustrated CCM enhances the metabolic adaptability of KRAS-mutant CRC cells to perturbations, emphasizing the importance of including TME components in metabolic modeling and therapeutic development and suggesting that targeting tumor-CAF metabolic interactions may improve treatment strategies.

Indexed as

Cancer-Associated FibroblastsColorectal NeoplasmsCell Line, TumorComputer SimulationGlycolysisHumansMetabolic ReprogrammingModels, BiologicalMutationPentose Phosphate PathwayProto-Oncogene Proteins p21(ras)Tumor MicroenvironmentKRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID41781387
PMCPMC13077082

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LicenceCC BY-NC-ND
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Registered trials

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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.