Evidence map›Paper›PMID 40894047›Full record

ArticleResearch square2025

Paclitaxel neurotoxicity is triggered by epidermal EG5-dependent microtubule fasciculation and X-ROS formation.

Chia-Jung Hsieh, Anthony M Cirrincione, Mikaela R Vlach, Antonio Cadiz Diaz, Natalie A Schmidt, Xin Li, Sergio Gutierrez, Marie J Ugo, Maria Celina Amaya Sanchez, Cassandra A Reimonn and 16 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

26 authors.

Chia-Jung HsiehDepartment of Biology, University of Miami, Coral Gables, Florida 33146, USA.
Anthony M CirrincioneDepartment of Biology, University of Miami, Coral Gables, Florida 33146, USA.
Mikaela R VlachDepartment of Biology, University of Miami, Coral Gables, Florida 33146, USA.ORCID https://orcid.org/0009-0005-1794-5312
Antonio Cadiz DiazDepartment of Biology, University of Miami, Coral Gables, Florida 33146, USA.ORCID https://orcid.org/0000-0001-8955-5544
Natalie A SchmidtDepartment of Biology, University of Miami, Coral Gables, Florida 33146, USA.ORCID https://orcid.org/0000-0001-7357-2841
Xin LiDepartment of Biology, University of Miami, Coral Gables, Florida 33146, USA.
Sergio GutierrezDepartment of Biology, University of Miami, Coral Gables, Florida 33146, USA.
Marie J UgoDepartment of Biology, University of Miami, Coral Gables, Florida 33146, USA.
Maria Celina Amaya SanchezDepartment of Cell Biology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.ORCID https://orcid.org/0000-0001-6150-3494
Cassandra A ReimonnUniversity of New England, Department of Biomedical Sciences, Biddeford, Maine, 04005.ORCID https://orcid.org/0009-0008-0835-7924
Stefan WuchtyDepartment of Biology, University of Miami, Coral Gables, Florida 33146, USA.ORCID https://orcid.org/0000-0001-8916-6522
Adriana D PellegriniMDI Biological Laboratory, Kathryn W. Davis Center for Regenerative Biology and Medicine, Bar Harbor, Maine 04762, USA.
Leah Rk RudeMDI Biological Laboratory, Kathryn W. Davis Center for Regenerative Biology and Medicine, Bar Harbor, Maine 04762, USA.
Leah G PappalardoMDI Biological Laboratory, Kathryn W. Davis Center for Regenerative Biology and Medicine, Bar Harbor, Maine 04762, USA.
Daniel P ReganDepartment of Chemical and Biomedical Engineering, University of Maine, Orono, Maine 04469, USA.ORCID https://orcid.org/0000-0002-6363-0144
Bowen ZhaoDepartment of Chemistry, Macdonald Foundation Biomedical Nanotechnology Institute, University of Miami, Coral Gables, Florida 33146, USA.ORCID https://orcid.org/0009-0001-5156-6739
Fuwu ZhangDepartment of Chemistry, Macdonald Foundation Biomedical Nanotechnology Institute, University of Miami, Coral Gables, Florida 33146, USA.ORCID https://orcid.org/0000-0002-1928-3472
Caitlin HowellDepartment of Chemical and Biomedical Engineering, University of Maine, Orono, Maine 04469, USA.ORCID https://orcid.org/0000-0002-9345-6642
Sybil HrstkaDepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USA.ORCID https://orcid.org/0000-0003-1442-5707
Surendra DasariDepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USA.ORCID https://orcid.org/0000-0002-7972-3556
Enrico CapobiancoThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.ORCID https://orcid.org/0000-0002-3532-1192
Thomas S LisseDepartment of Biology, University of Miami, Coral Gables, Florida 33146, USA.ORCID https://orcid.org/0000-0001-5557-3904
Benjamin J HarrisonUniversity of New England, Department of Biomedical Sciences, Biddeford, Maine, 04005.
Nathan P StaffDepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USA.ORCID https://orcid.org/0000-0001-6760-3859
Mike Xiangxi XuDepartment of Cell Biology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.ORCID https://orcid.org/0000-0003-2886-5308
Sandra RiegerDepartment of Biology, University of Miami, Coral Gables, Florida 33146, USA.ORCID https://orcid.org/0000-0002-9059-1670

Funding

The Maine Biomedical Research Network (INBRE)P20GM103423 · NIGMS · MOUNT DESERT ISLAND BIOLOGICAL LAB · PI Dustin Lynn Updike · 2012 to 2026
$60.0M
Understanding the role of thyroid hormone signaling during axolotl limb regenerationP20GM104318 · NIGMS · MOUNT DESERT ISLAND BIOLOGICAL LAB · PI DRUMMOND, IAIN A. · 2013 to 2023
$23.0M
Investigating the role of MAP2 in chemotherapy-induced peripheral neurotoxicityR01CA275870 · NCI · MAYO CLINIC ROCHESTER · PI Nathan P Staff · 2023 to 2026
$2.4M
Assessment of Chemotherapy-Induced Peripheral Neuropathy Susceptibility Using Patient-derived iPSC TechnologyR01CA211887 · NCI · MAYO CLINIC ROCHESTER · PI STAFF, NATHAN P · 2017 to 2021
$1.8M
(PQ 9) Dysregulation of epidermal MMP-13 as cause of paclitaxel-induced peripheral neuropathyR01CA215973 · NCI · UNIVERSITY OF MIAMI CORAL GABLES · PI RIEGER, SANDRA · 2017 to 2021
$1.7M
Analyzing paclitaxel-induced changes in the skin as possible cause of CIPNR21NS094939 · NINDS · MOUNT DESERT ISLAND BIOLOGICAL LAB · PI RIEGER, SANDRA · 2016 to 2016
$249k
NCI NIH HHS R01 CA211887NCI NIH HHS R01 CA215973NCI NIH HHS R01 CA275870NIGMS NIH HHS P20 GM103423NIGMS NIH HHS P20 GM104318NINDS NIH HHS R21 NS094939
6 · The paper itself

Abstract

Taxanes are frontline chemotherapeutics that stabilize microtubules, induce mitotic arrest, and drive tumor remission. However, their off-target effects in healthy tissues, most notably cutaneous axon degeneration underlying chemotherapy-induced peripheral neuropathy (CIPN), remain poorly understood. Here, we show that paclitaxel induces microtubule fasciculation in epidermal keratinocytes through the mitotic kinesin Eg5, thereby initiating CIPN. Mechanistically, paclitaxel enhances Eg5-dependent fasciculation of detyrosinated (stabilized) microtubules, which constrict and breach the nuclear lamina. This deformation triggers tension-dependent NADPH oxidase-mediated nuclear ROS (X-ROS) formation upstream of

Indexed as

C57BLcell cycledetyrosinationEg5fasciculationkeratinocyteKif11Kinesin-5micemicrotubulesMMP13nucleuspaclitaxelpatientperipheral neuropathyTaxolzebrafish

Identifiers

PMID40894047
PMCPMC12393485

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.