Evidence map›Paper›PMID 31658996›Full record

ArticleMolecular and cellular biology2020

The SOX9-Aldehyde Dehydrogenase Axis Determines Resistance to Chemotherapy in Non-Small-Cell Lung Cancer.

Maria A Voronkova, Liying W Rojanasakul, Chayanin Kiratipaiboon, Yon Rojanasakul

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.2field-weighted citation impact, top 10% 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

28 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. The Significance of Aldehyde Dehydrogenase 1 in Cancers.International journal of molecular sciences · 2024
    Review
  10. Article
  11. ALDEFLUOR activity, ALDH isoforms, and their clinical significance in cancers.Journal of enzyme inhibition and medicinal chemistry · 2023
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Prognostic value ofFrontiers in genetics · 2022
    Article
  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

4 authors at 2 institutions in 1 country.

Maria A VoronkovaWest Virginia University Cancer Institute, West Virginia University, Morgantown, West Virginia, USA.
Liying W RojanasakulAllergy and Clinical Immunology Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA.
Chayanin KiratipaiboonDepartment of Pharmaceutical Sciences, West Virginia University, Morgantown, West Virginia, USA.
Yon RojanasakulWest Virginia University Cancer Institute, West Virginia University, Morgantown, West Virginia, USA yrojan@hsc.wvu.edu.
West Virginia University · USNational Institute for Occupational Safety and Health · US

Funding

WV INBRE: The Inhibitor of Growth Family Member 4 (ING4) inhibits L-Type Amino Acid Transporter 1 (LAT1) expression to suppress Breast CancerP20GM103434 · NIGMS · MARSHALL UNIVERSITY · PI GARY O RANKIN · 2012 to 2026
$61.1M
THE ROLE OF HEF1 PROTEIN IN INVASION OF METASTATIC BREAST CANCERP20RR016440 · NCRR · WEST VIRGINIA UNIVERSITY · PI HARNER, JAMES · 2001 to 2010
$22.8M
West Virginia Flow Cytometry Core FacilityP30GM103488 · NIGMS · WEST VIRGINIA UNIVERSITY · PI CUFF, CHRISTOPHER F · 2012 to 2016
$4.8M
Induction of Neoplastic Transformation and Cancer Stem Cells by Carbon NanotubesR01ES022968 · NIEHS · WEST VIRGINIA UNIVERSITY · PI ROJANASAKUL, YON · 2014 to 2019
$1.7M
Nanoparticle Fibrogenicity and Fibroblast Stem-Like CellsR01EB018857 · NIBIB · WEST VIRGINIA UNIVERSITY · PI ROJANASAKUL, YON · 2016 to 2019
$1.3M
COBRE FOR SIGNAL TRANSDUCTION AND CANCER PHASE IIIP30RR032138 · NCRR · WEST VIRGINIA UNIVERSITY · PI GIBSON, LAURA F. · 2011 to 2011
$1.1M
Special Becton Dickinson Fortessa Flow CytometerS10OD016165 · OD · WEST VIRGINIA UNIVERSITY · PI CUFF, CHRISTOPHER F · 2013 to 2013
$384k
NCRR NIH HHS P20 RR016440NCRR NIH HHS P30 RR032138NIBIB NIH HHS R01 EB018857NIEHS NIH HHS R01 ES022968NIGMS NIH HHS P20 GM103434NIGMS NIH HHS P30 GM103488NIH HHS S10 OD016165
6 · The paper itself

Abstract

Chemotherapy resistance and tumor relapse are the major contributors to low patient survival, and both have been largely attributed to cancer stem-like cells (CSCs) or tumor-initiating cells (TICs). Moreover, most conventional therapies are not effective against CSCs, which necessitates the discovery of CSC-specific biomarkers and drug targets. Here, we demonstrated that the embryonic transcription factor SOX9 is an important regulator of acquired chemoresistance in non-small-cell lung cancer (NSCLC). Our results show that SOX9 expression is elevated in NSCLC cells after treatment with the chemotherapeutic cisplatin and that overexpression of SOX9 correlates with worse overall survival in lung cancer patients. We further demonstrated that SOX9 knockdown increases cellular sensitivity to cisplatin, whereas its overexpression promotes drug resistance. Moreover, this transcription factor promotes the stem-like properties of NSCLC cells and increases their aldehyde dehydrogenase (ALDH) activity, which was identified to be the key mechanism of SOX9-induced chemoresistance. Finally, we showed that ALDH1A1 is a direct transcriptional target of SOX9, based on chromatin immunoprecipitation and luciferase reporter assays. Taken together, our novel findings on the role of the SOX9-ALDH axis support the use of this CSC regulator as a prognostic marker of cancer chemoresistance and as a potential drug target for CSC therapy.

Indexed as

A549 CellsAldehyde Dehydrogenase 1 FamilyAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCell Line, TumorCisplatinDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansLung NeoplasmsRetinal DehydrogenaseSOX9 Transcription FactorUp-RegulationAldehyde Dehydrogenase 1 FamilyALDH1A1 protein, humanAntineoplastic AgentsCisplatinRetinal DehydrogenaseSOX9 protein, humanSOX9 Transcription FactorALDH1A1cancer stem-like cellschemoresistanceSOX9

Identifiers

PMID31658996
PMCPMC6944474
OpenAlexW2981449347

What OpenQuestion holds

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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.