Evidence map›Paper›PMID 41423506›Full record

ArticleBritish journal of cancer2026

Effects of mitotically active polyploid giant cancer cells on chemoresistance through interaction with cancer-associated fibroblasts.

Go Itoh, Yuma Fukushi, Kurara Takagane, Keisuke Kanetaka, Hitomi Suzuki, Yohei Kawasaki, Sei Kuriyama, Kenji Iemura, Kozo Tanaka, Akiteru Goto and 1 more

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Article in British journal of cancer, 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.

Go ItohDepartment of Molecular Medicine and Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
Yuma FukushiDepartment of Molecular Medicine and Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
Kurara TakaganeDepartment of Molecular Medicine and Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
Keisuke KanetakaDepartment of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan.
Hitomi SuzukiDepartment of Otorhinolaryngology and Head-and-Neck Surgery, Akita University Graduate School of Medicine, Akita, Japan.
Yohei KawasakiDepartment of Otorhinolaryngology and Head-and-Neck Surgery, Akita University Graduate School of Medicine, Akita, Japan.
Sei KuriyamaDepartment of Molecular Medicine and Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
Kenji IemuraDepartment of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
Kozo TanakaDepartment of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.ORCID http://orcid.org/0000-0001-6086-2858
Akiteru GotoDepartment of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan.ORCID http://orcid.org/0000-0001-8776-9004
Masamitsu TanakaDepartment of Molecular Medicine and Biochemistry, Akita University Graduate School of Medicine, Akita, Japan. mastanak@med.akita-u.ac.jp.ORCID http://orcid.org/0000-0002-4823-9737

Funding

Princess Takamatsu Cancer Research Fund 19-25123
6 · The paper itself

Abstract

backgroundPolyploid giant cancer cells (PGCCs), characterized by enlarged or multiple nuclei, have long been considered non-proliferative and hallmarks of high malignancy. However, their functional contribution to tumor progression remains unclear.

methodsWe identified and characterized a subset of mitotically active (MA)-PGCCs in human oral squamous cell carcinoma specimens and cell lines. Mitotic activity and cell cycle was assessed using immunofluorescence, time-lapse microscopy and FUCCI. We evaluated the interactions between MA-PGCCs and cancer-associated fibroblasts (CAFs), focusing on transforming growth factor-beta (TGF-β) signaling. Chemoresistance to 5-fluorouracil (5-FU) was analyzed using cell viability assays.

resultsMA-PGCCs exhibited both bipolar and multipolar mitosis, generating heterogeneous progeny that contributed to genomic instability. These cells increased the number of CAFs with elevated TGF-β expression, promoting epithelial-mesenchymal transition (EMT) and enhancing resistance to 5-FU. Mechanistically, enhanced reactive oxygen species in MA-PGCCs upregulated urokinase-type plasminogen activator (uPA) and its receptor uPAR, promoting plasmin-mediated activation of TGF-β secreted from adjacent CAFs. Upregulation of TGF-β receptors in MA-PGCCs further amplified TGF-β signaling, accelerating EMT.

conclusionsOur findings identify MA-PGCCs as a proliferative subpopulation that promotes EMT and chemoresistance through a TGF-β-uPA/uPAR feedback loop. Targeting this pathway may offer a novel therapeutic strategy for the treatment of aggressive tumors enriched in MA-PGCCs.

Indexed as

Cancer-Associated FibroblastsCarcinoma, Squamous CellDrug Resistance, NeoplasmGiant CellsMitosisMouth NeoplasmsPolyploidyCell Line, TumorEpithelial-Mesenchymal TransitionFluorouracilHumansReactive Oxygen SpeciesSignal TransductionTransforming Growth Factor betaFluorouracilReactive Oxygen SpeciesTransforming Growth Factor beta

Identifiers

PMID41423506
PMCPMC12905402

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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.