Evidence map›Paper›PMID 42241284›Full record

ArticleCell reports2026

Cisplatin resistance in an ovarian cancer model is mediated by microtubule dynamics regulator TPPP3 in synergy with tubulin code rewiring.

Sachi Horibata, Kishore K Mahalingan, Ruchi Patel, Yu Fan, Jordan M Hotz, Adriana Ponton-Almodovar, Keith MacRenaris, Yan Li, Daoud Meerzaman, Michael M Gottesman and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Sachi HoribataLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Precision Health Program, Michigan State University, East Lansing, MI 48824, USA; Cell and Molecular Biology Program, Michigan State University, East Lansing, MI 48824, USA; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA. Electronic address: horibat2@msu.edu.
Kishore K MahalinganCell Biology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Ruchi PatelLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yu FanComputational Genomics and Bioinformatics Branch, Center for Biomedical Informatics & Information Technology, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
Jordan M HotzLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Adriana Ponton-AlmodovarPrecision Health Program, Michigan State University, East Lansing, MI 48824, USA; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA.
Keith MacRenarisQuantitative Bio Element Analysis and Mapping (QBEAM) Center, Michigan State University, East Lansing, MI 48824, USA.
Yan LiProteomics Core, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Daoud MeerzamanComputational Genomics and Bioinformatics Branch, Center for Biomedical Informatics & Information Technology, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
Michael M GottesmanLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: mgottesman@nih.gov.
Antonina Roll-MecakCell Biology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; Biochemistry and Biophysics Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: antonina@mail.nih.gov.

Funding

Readout of the tubulin code by cellular effectorsZIANS003164 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI ROLL-MECAK, ANTONINA · 2017 to 2025
$11.7M
Mechanism of tubulin modification enzymesZIANS003163 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI ROLL-MECAK, ANTONINA · 2017 to 2025
$10.8M
TR&D Project 3: Photoacoustic Detection of Metal Fluxes at the Tissue LevelP41GM135018 · NIGMS · NORTHWESTERN UNIVERSITY · PI JACOBSEN, CHRIS JOHNSON, O'HALLORAN, THOMAS V · 2020 to 2024
$5.8M
Intramural NIH HHS ZIA NS003163Intramural NIH HHS ZIA NS003164NIGMS NIH HHS P41 GM135018
6 · The paper itself

Abstract

Cisplatin is a mainstay in cancer treatment, but toxicity and resistance limit its potential. Using RNA sequencing (RNA-seq), we show that ovarian cancer cells undergo broad changes in the microtubule cytoskeleton that correlate with resistance. Consistent with this, we find that cisplatin directly impacts microtubule dynamics in vitro and in cells. Paclitaxel counteracts cisplatin and increases resistance. By purifying tubulin from cisplatin-sensitive, -resistant, and -re-sensitized ovarian cancer cells, we demonstrate that resistance acquisition rewires the tubulin code, leading to microtubule stabilization. Furthermore, tubulin polymerization-promoting protein 3 (TPPP3) contributes to resistance. In vitro, TPPP3 synergizes with tubulin isotypes from resistant cells to yield maximal microtubule stabilization in response to cisplatin. Database analysis shows that patients with low TPPP3 levels have improved therapeutic outcome. Our findings implicate TPPP3 and microtubule dysregulation in cisplatin resistance, independent of effects through DNA damage, and have bearing on the etiology of cisplatin-associated neuropathies and ototoxicity.

Indexed as

CisplatinDrug Resistance, NeoplasmMicrotubulesNerve Tissue ProteinsOvarian NeoplasmsTubulinAntineoplastic AgentsCell Line, TumorFemaleHumansPaclitaxelAntineoplastic AgentsCisplatinNerve Tissue ProteinsPaclitaxelTPPP protein, humanTubulincancerchemoresistancecisplatinCP: cancerCP: cell biologymicrotubule dynamicsmicrotubule targeting agentsovarian cancertaxolTPPP3tubulin codetubulin isotypes

Identifiers

PMID42241284
PMCPMC13615893

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.