Evidence map›Paper›PMID 39693448›Full record

ArticleScience advances2024

Mechanosensitive nuclear uptake of chemotherapy.

Nicholas R Scott, Sowon Kang, Sapun H Parekh

Abstract read
In one paragraph

Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. 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

3 authors.

Nicholas R ScottDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.ORCID 0000-0002-7096-5217
Sowon KangDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.ORCID 0009-0001-8911-0841
Sapun H ParekhDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.ORCID 0000-0001-8522-1854

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The nucleus is at the nexus of mechanotransduction and the final barrier for most first line chemotherapeutics. Here, we study the intersection between nuclear-cytoskeletal coupling and chemotherapy nuclear internalization. We find that chronic and acute modulation of intracellular filaments changes nuclear influx of doxorubicin (DOX). Rapid changes in cell strain by disruption of cytoskeletal and nuclear filaments sensitize nuclei to DOX, whereas chronic reduction of cell strain desensitize nuclei to DOX. Extracted nuclei from invasive cancer cells lines from different tissues have distinct nuclear permeability to DOX. Last, we show that mechano-priming of cells by paclitaxel markedly improves DOX nuclear internalization, rationalizing the observed drug synergies. Our findings reveal that nuclear uptake is a critical, previously unquantified aspect of drug resistance. With nuclear permeability to chemotherapy being tunable via modulation of nuclear mechanotransduction, mechano-priming may be useful to help overcome drug resistance in the future.

Indexed as

Cell NucleusDoxorubicinMechanotransduction, CellularAntineoplastic AgentsCell Line, TumorCytoskeletonDrug Resistance, NeoplasmHumansNeoplasmsPaclitaxelAntineoplastic AgentsDoxorubicinPaclitaxel

Identifiers

PMID39693448
PMCPMC11654694

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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.