Evidence map›Paper›PMID 35313064›Full record

ArticleMolecular oncology2022

KSR induces RAS-independent MAPK pathway activation and modulates the efficacy of KRAS inhibitors.

Guillem Paniagua, Harrys K C Jacob, Oksana Brehey, Sara García-Alonso, Carmen G Lechuga, Tirso Pons, Monica Musteanu, Carmen Guerra, Matthias Drosten, Mariano Barbacid

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.3field-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

22 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Proteomics in pancreatic cancer.Biomarker research · 2025
    Review
  11. Review
  12. Review
  13. KSR1 Knockout Mouse Model Demonstrates MAPK Pathway's Key Role in Cisplatin- and Noise-induced Hearing Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  14. Review
  15. SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  16. Article
  17. Review
  18. 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

10 authors at 3 institutions in 1 country.

Guillem PaniaguaExperimental Oncology, Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Harrys K C JacobExperimental Oncology, Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Oksana BreheyExperimental Oncology, Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Sara García-AlonsoExperimental Oncology, Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Carmen G LechugaExperimental Oncology, Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Tirso PonsDepartment of Immunology and Oncology, National Center for Biotechnology (CNB-CSIC), Spanish National Research Council, Madrid, Spain.
Monica MusteanuExperimental Oncology, Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Carmen GuerraExperimental Oncology, Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Matthias DrostenExperimental Oncology, Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.ORCID 0000-0002-3205-456X
Mariano BarbacidExperimental Oncology, Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.ORCID 0000-0002-1480-2624
Spanish National Cancer Research Centre · ESConsejo Superior de Investigaciones Científicas · ESUniversidad Complutense de Madrid · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The kinase suppressor of rat sarcoma (RAS) proteins (KSR1 and KSR2) have long been considered as scaffolding proteins required for optimal mitogen-activated protein kinase (MAPK) pathway signalling. However, recent evidence suggests that they play a more complex role within this pathway. Here, we demonstrate that ectopic expression of KSR1 or KSR2 is sufficient to activate the MAPK pathway and to induce cell proliferation in the absence of RAS proteins. In contrast, the ectopic expression of KSR proteins is not sufficient to induce cell proliferation in the absence of either rapidly accelerated fibrosarcoma (RAF) or MAPK-ERK kinase proteins, indicating that they act upstream of RAF. Indeed, KSR1 requires dimerization with at least one member of the RAF family to stimulate proliferation, an event that results in the translocation of the heterodimerized RAF protein to the cell membrane. Mutations in the conserved aspartic acid-phenylalanine-glycine motif of KSR1 that affect ATP binding impair the induction of cell proliferation. We also show that increased expression levels of KSR1 decrease the responsiveness to the KRAS

Indexed as

Mitogen-Activated Protein KinasesProto-Oncogene Proteins p21(ras)Genes, rasHumansMitogen-Activated Protein Kinase KinasesProtein KinasesSignal TransductionKRAS protein, humanKSR-1 protein kinaseMitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesProtein KinasesProto-Oncogene Proteins p21(ras)ATP bindingKRASG12CMAPK pathwayRAS-independent proliferationresistancesotorasib

Identifiers

PMID35313064
PMCPMC9441002
OpenAlexW4220687313

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.