Evidence map›Paper›PMID 27876874›Full record

ArticleScientific reports2016

TWIST1 drives cisplatin resistance and cell survival in an ovarian cancer model, via upregulation of GAS6, L1CAM, and Akt signalling.

Cai M Roberts, Michelle A Tran, Mary C Pitruzzello, Wei Wen, Joana Loeza, Thanh H Dellinger, Gil Mor, Carlotta A Glackin

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

46 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Subcellular Stress Markers in Epithelial Ovarian Cancer.International journal of molecular sciences · 2025
    Review
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  18. L1CAM promotes ovarian cancer stemness and tumor initiation via FGFR1/SRC/STAT3 signaling.Journal of experimental & clinical cancer research : CR · 2021
    Article
  19. 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

8 authors at 4 institutions in 1 country.

Cai M RobertsDepartment of Developmental and Stem Cell Biology, 1500 E. Duarte Road Duarte, CA 91010, USA.
Michelle A TranDepartment of Developmental and Stem Cell Biology, 1500 E. Duarte Road Duarte, CA 91010, USA.
Mary C PitruzzelloDivision of Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Wei WenDepartment of Surgery, Division of Gynaecologic Oncology, City of Hope Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA.
Joana LoezaCalifornia State University, Los Angeles, 5151 State University Drive, Los Angeles, CA 90032, USA.
Thanh H DellingerDepartment of Surgery, Division of Gynaecologic Oncology, City of Hope Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA.
Gil MorDivision of Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Carlotta A GlackinDepartment of Developmental and Stem Cell Biology, 1500 E. Duarte Road Duarte, CA 91010, USA.
Yale University · USCity of Hope · USCity Of Hope National Medical Center · USCalifornia State University Los Angeles · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA033572
6 · The paper itself

Abstract

Epithelial ovarian cancer (EOC) is the most deadly gynaecologic malignancy due to late onset of symptoms and propensity towards drug resistance. Epithelial-mesenchymal transition (EMT) has been linked to the development of chemoresistance in other cancers, yet little is known regarding its role in EOC. In this study, we sought to determine the role of the transcription factor TWIST1, a master regulator of EMT, on cisplatin resistance in an EOC model. We created two Ovcar8-derived cell lines that differed only in their TWIST1 expression. TWIST1 expression led to increased tumour engraftment in mice, as well as cisplatin resistance in vitro. RNA sequencing analysis revealed that TWIST1 expression resulted in upregulation of GAS6 and L1CAM and downregulation of HMGA2. Knockdown studies of these genes demonstrated that loss of GAS6 or L1CAM sensitized cells to cisplatin, but that loss of HMGA2 did not give rise to chemoresistance. TWIST1, in part via GAS6 and L1CAM, led to higher expression and activation of Akt upon cisplatin treatment, and inhibition of Akt activation sensitized cells to cisplatin. These results suggest TWIST1- and EMT-driven increase in Akt activation, and thus tumour cell proliferation, as a potential mechanism of drug resistance in EOC.

Indexed as

AnimalsCell Line, TumorCell SurvivalCisplatinDrug Resistance, NeoplasmEnzyme ActivationFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesGrowth Arrest-Specific Protein 6HMGA2 ProteinHumansIntercellular Signaling Peptides and ProteinsMiceModels, BiologicalNeural Cell Adhesion Molecule L1CisplatinGrowth Arrest-Specific Protein 6HMGA2 ProteinIntercellular Signaling Peptides and ProteinsNeural Cell Adhesion Molecule L1Nuclear ProteinsProto-Oncogene Proteins c-aktRNA, Small InterferingTWIST1 protein, humanTwist-Related Protein 1

Identifiers

PMID27876874
PMCPMC5120297
OpenAlexW2554936259

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.