Evidence map›Paper›PMID 31133691›Full record

ArticleBritish journal of cancer2019

Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRAS

Theodosia Charitou, Sriganesh Srihari, Miriam A Lynn, Mohamed-Ali Jarboui, Erik Fasterius, Max Moldovan, Senji Shirasawa, Toshiyuki Tsunoda, Marius Ueffing, Jianling Xie and 7 more

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

36 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. The permissive binding theory of cancer.Frontiers in oncology · 2023
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Effect ofFrontiers in cell and developmental biology · 2022
    Article
  19. Review
  20. Article
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

17 authors at 8 institutions in 5 countries.

Theodosia CharitouEMBL Australia Group, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA, 5000, Australia.
Sriganesh SrihariEMBL Australia Group, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA, 5000, Australia.
Miriam A LynnEMBL Australia Group, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA, 5000, Australia.
Mohamed-Ali JarbouiInstitute for Ophthalmic Research, University of Tübingen, Tübingen, Germany.
Erik FasteriusSchool of Biotechnology, Royal Institute of Technology, Stockholm, Sweden.
Max MoldovanEMBL Australia Group, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA, 5000, Australia.
Senji ShirasawaFaculty of Medicine, Fukuoka University, Fukuoka, Fukuoka Prefecture, 814-0133, Japan.
Toshiyuki TsunodaFaculty of Medicine, Fukuoka University, Fukuoka, Fukuoka Prefecture, 814-0133, Japan.
Marius UeffingInstitute for Ophthalmic Research, University of Tübingen, Tübingen, Germany.
Jianling XieNutrition, Diabetes & Metabolism, South Australian Health & Medical Research Institute, Adelaide, SA, 5000, Australia.
Jin XinNutrition, Diabetes & Metabolism, South Australian Health & Medical Research Institute, Adelaide, SA, 5000, Australia.
Xuemin WangNutrition, Diabetes & Metabolism, South Australian Health & Medical Research Institute, Adelaide, SA, 5000, Australia.
Christopher G ProudNutrition, Diabetes & Metabolism, South Australian Health & Medical Research Institute, Adelaide, SA, 5000, Australia.
Karsten BoldtInstitute for Ophthalmic Research, University of Tübingen, Tübingen, Germany.
Cristina Al-Khalili SzigyartoSchool of Biotechnology, Royal Institute of Technology, Stockholm, Sweden.
Walter KolchSystems Biology Ireland, University College Dublin, Dublin, Ireland.
David J LynnEMBL Australia Group, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA, 5000, Australia. david.lynn@sahmri.com.
EMBL Australia · AUSouth Australian Health and Medical Research Institute · AUUniversity of Tübingen · DEFukuoka University · JPKTH Royal Institute of Technology · SEFlinders University · AUUniversity College Dublin · IEUniversity of Adelaide · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundActivating mutations in KRAS frequently occur in colorectal cancer (CRC) patients, leading to resistance to EGFR-targeted therapies.

methodsTo better understand the cellular reprogramming which occurs in mutant KRAS cells, we have undertaken a systems-level analysis of four CRC cell lines which express either wild type (wt) KRAS or the oncogenic KRAS

resultsRNAseq revealed that genes involved in ribosome biogenesis, mRNA translation and metabolism were significantly upregulated in mtKRAS cells. Consistent with the transcriptional data, protein synthesis and cell proliferation were significantly higher in the mtKRAS cells. Targeted metabolomics analysis also confirmed the metabolic reprogramming in mtKRAS cells. Interestingly, mtKRAS cells were highly transcriptionally responsive to EGFR activation by TGFα stimulation, which was associated with an unexpected downregulation of genes involved in a range of anabolic processes. While TGFα treatment strongly activated protein synthesis in wtKRAS cells, protein synthesis was not activated above basal levels in the TGFα-treated mtKRAS cells. This was likely due to the defective activation of the mTORC1 and other pathways by TGFα in mtKRAS cells, which was associated with impaired activation of PKB signalling and a transient induction of AMPK signalling.

conclusionsWe have found that mtKRAS cells are substantially rewired at the transcriptional, translational and metabolic levels and that this rewiring may reveal new vulnerabilities in oncogenic KRAS CRC cells that could be exploited in future.

Indexed as

MutationTranscription, GeneticAMP-Activated Protein KinasesCell Line, TumorColorectal NeoplasmsErbB ReceptorsHumansMechanistic Target of Rapamycin Complex 1MetabolomicsProto-Oncogene Proteins p21(ras)RibosomesSignal TransductionTransforming Growth Factor alphaAMP-Activated Protein KinasesErbB ReceptorsKRAS protein, humanMechanistic Target of Rapamycin Complex 1Proto-Oncogene Proteins p21(ras)Transforming Growth Factor alpha

Identifiers

PMID31133691
PMCPMC6738113
OpenAlexW2947664300

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.