Evidence map›Paper›PMID 25961928›Full record

ArticleOncogene2016

Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance.

P Khongkow, A R Gomes, C Gong, E P S Man, J W-H Tsang, F Zhao, L J Monteiro, R C Coombes, R H Medema, U S Khoo and 1 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
142citing papers in PubMed, 3 pooled it
8.7field-weighted citation impact, top 2% 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

142 citing papers in PubMed, 3 syntheses or guidelines pooled it, 248 citations in OpenAlex.

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  18. Phytochemical combinations of lichenFrontiers in pharmacology · 2025
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82 more citing papers are in PubMed but not listed here.

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 at 5 institutions in 4 countries.

P KhongkowDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
A R GomesDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
C GongDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
E P S ManDepartment of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
J W-H TsangDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
F ZhaoDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
L J MonteiroDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
R C CoombesDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
R H MedemaDivision of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
U S KhooDepartment of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
E W-F LamDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
University of Hong Kong · HKHammersmith Hospital · GBImperial College London · GBChinese University of Hong Kong · CNThe Netherlands Cancer Institute · NL

Funding

Biotechnology and Biological Sciences Research Council BBS/B/03785Breast Cancer Now 2012MAYPR070Breast Cancer Now 2012NOVPHD016Cancer Research UK 12011Cancer Research UK A12011
6 · The paper itself

Abstract

FOXM1 has been implicated in taxane resistance, but the molecular mechanism involved remains elusive. In here, we show that FOXM1 depletion can sensitize breast cancer cells and mouse embryonic fibroblasts into entering paclitaxel-induced senescence, with the loss of clonogenic ability, and the induction of senescence-associated β-galactosidase activity and flat cell morphology. We also demonstrate that FOXM1 regulates the expression of the microtubulin-associated kinesin KIF20A at the transcriptional level directly through a Forkhead response element (FHRE) in its promoter. Similar to FOXM1, KIF20A expression is downregulated by paclitaxel in the sensitive MCF-7 breast cancer cells and deregulated in the paclitaxel-resistant MCF-7Tax(R) cells. KIF20A depletion also renders MCF-7 and MCF-7Tax(R) cells more sensitive to paclitaxel-induced cellular senescence. Crucially, resembling paclitaxel treatment, silencing of FOXM1 and KIF20A similarly promotes abnormal mitotic spindle morphology and chromosome alignment, which have been shown to induce mitotic catastrophe-dependent senescence. The physiological relevance of the regulation of KIF20A by FOXM1 is further highlighted by the strong and significant correlations between FOXM1 and KIF20A expression in breast cancer patient samples. Statistical analysis reveals that both FOXM1 and KIF20A protein and mRNA expression significantly associates with poor survival, consistent with a role of FOXM1 and KIF20A in paclitaxel action and resistance. Collectively, our findings suggest that paclitaxel targets the FOXM1-KIF20A axis to drive abnormal mitotic spindle formation and mitotic catastrophe and that deregulated FOXM1 and KIF20A expression may confer paclitaxel resistance. These findings provide insights into the underlying mechanisms of paclitaxel resistance and have implications for the development of predictive biomarkers and novel chemotherapeutic strategies for paclitaxel resistance.

Indexed as

Down-RegulationDrug Resistance, NeoplasmMitosisAnimalsAntineoplastic AgentsBreast NeoplasmsCell SurvivalCellular SenescenceFemaleForkhead Box Protein M1Forkhead Transcription FactorsGene Expression Regulation, NeoplasticHumansKinesinsMicePaclitaxelAntineoplastic AgentsForkhead Box Protein M1Forkhead Transcription FactorsFOXM1 protein, humanKIF20A protein, humanKinesinsPaclitaxel

Identifiers

PMID25961928
PMCPMC4538879
OpenAlexW1955107491

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.