Evidence map›Paper›PMID 33287446›Full record

ArticleInternational journal of molecular sciences2020

Insight into Cisplatin-Resistance Signaling of W1 Ovarian Cancer Cells Emerges mTOR and HSP27 as Targets for Sensitization Strategies.

Kathleen Wantoch von Rekowski, Philipp König, Svenja Henze, Martin Schlesinger, Piotr Zawierucha, Radosław Januchowski, Gerd Bendas

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

11 citing papers in PubMed, 16 citations in OpenAlex.

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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

7 authors at 3 institutions in 2 countries.

Kathleen Wantoch von RekowskiDepartment of Pharmacy, University of Bonn, 53113 Bonn, Germany.
Philipp KönigDepartment of Pharmacy, University of Bonn, 53113 Bonn, Germany.
Svenja HenzeDepartment of Pharmacy, University of Bonn, 53113 Bonn, Germany.
Martin SchlesingerDepartment of Pharmacy, University of Bonn, 53113 Bonn, Germany.
Piotr ZawieruchaDepartment of RNA Metabolism, Institute of Bioorganic Chemistry Polish Academy of Sciences, 61-704 Poznań, Poland.
Radosław JanuchowskiInstitute of Health Sciences, Collegium Medicum, University of Zielona Gora, Zyty 28 St., 65-046 Zielona Góra, Poland.ORCID 0000-0001-7286-0657
Gerd BendasDepartment of Pharmacy, University of Bonn, 53113 Bonn, Germany.
University of Bonn · DEInstitute of Bioorganic Chemistry, Polish Academy of Sciences · PLUniversity of Zielona Góra · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The microenvironment possesses a strong impact on the tumor chemoresistance when cells bind to components of the extracellular matrix. Here we elucidate the signaling pathways of cisplatin resistance in W1 ovarian cancer cells binding to collagen type 1 (COL1) and signaling interference with constitutive cisplatin resistance in W1CR cells to discover the targets for sensitization. Proteome kinase arrays and Western blots were used to identify the signaling components, their impact on cisplatin resistance was evaluated by inhibitory or knockdown approaches. W1 cell binding to COL1 upregulates integrin-associated signals via FAK/PRAS40/mTOR, confirmed by β1-integrin (ITGB1) knockdown. mTOR appears as key for resistance, its blockade reversed COL1 effects on W1 cell resistance completely. W1CR cells compensate ITGB1-knockdown by upregulation of discoidin domain receptor 1 (DDR1) as alternative COL1 sensor. COL1 binding via DDR1 activates the MAPK pathway, of which JNK1/2 appears critical for COL1-mediated resistance. JNK1/2 inhibition inverts COL1 effects in W1CR cells, whereas intrinsic cisplatin resistance remained unaffected. Remarkably, knockdown of HSP27, another downstream MAPK pathway component overcomes intrinsic resistance completely sensitizing W1CR cells to the level of W1 cells for cisplatin cytotoxicity. Our data confirm the independent regulation of matrix-induced and intrinsic chemoresistance in W1 ovarian cancer cells and offer novel targets for sensitization.

Indexed as

Drug Resistance, NeoplasmCaspasesCell Line, TumorCisplatinCollagen Type IDiscoidin Domain Receptor 1FemaleHSP27 Heat-Shock ProteinsHumansJNK Mitogen-Activated Protein KinasesMatrix MetalloproteinasesOvarian NeoplasmsPhosphatidylinositol 3-KinasesProtein BindingProto-Oncogene Proteins c-aktSignal TransductionCaspasesCisplatinCollagen Type IDiscoidin Domain Receptor 1HSP27 Heat-Shock ProteinsJNK Mitogen-Activated Protein KinasesMatrix MetalloproteinasesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesCAM-DRchemoresistancecisplatincollagenHSP27ovarian cancer

Identifiers

PMID33287446
PMCPMC7730285
OpenAlexW3106969911

What OpenQuestion holds

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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.