Evidence map›Paper›PMID 42031726›Full record

ArticleCell death & disease2026

βIII-tubulin can act as a brake on extrinsic apoptosis in pancreatic cancer.

George Sharbeen, John Kokkinos, Grace Schulstad, Elvis Pandzic, Janet Youkhana, Zerong Ma, Rosa Mistica C Ignacio, Aparna S Raina, Shannon Chiang, Cyrille Boyer and 23 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. PANoptosis and Immune Remodeling in the Tumor Microenvironment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  3. 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

33 authors.

George Sharbeen *Pancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia. g.sharbeen@unsw.edu.au.ORCID http://orcid.org/0000-0002-6373-1930
John Kokkinos *Pancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Grace SchulstadPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Elvis PandzicKatharina Gaus Light Microscopy Facility, Mark Wainwright Analytical Centre, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Janet YoukhanaPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Zerong MaChildren's Cancer Institute, Health Translation Hub, UNSW Sydney, Sydney, NSW, Australia.
Rosa Mistica C IgnacioAustralian Centre for NanoMedicine, UNSW Sydney, Sydney, NSW, Australia.
Aparna S RainaPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Shannon ChiangPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Cyrille BoyerAustralian Centre for NanoMedicine, UNSW Sydney, Sydney, NSW, Australia.
Koroush S HaghighiPrince of Wales Hospital, School of Clinical Medicine, Randwick Clinical Campus, UNSW Sydney, Sydney, NSW, Australia.
Matthew GunawarmanPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
David GoldsteinPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Val GebskiNHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia.
Marina PajicThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-3871-3829
Meagan E DavisPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Oliver S M ArkellPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-5228-0919
Chantal KopeckySchool of Chemistry, UNSW Sydney, Sydney, NSW, Australia.
Estrella Gonzales-AloyChildren's Cancer Institute, Health Translation Hub, UNSW Sydney, Sydney, NSW, Australia.
Alexander IshakPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Mert ErkanMehmet Ali Aydinlar Acibadem University, Atasehir Hospital, Istanbul, Turkey.
Jennifer P MortonSchool of Cancer Sciences, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0001-5766-9141
Maria KavallarisAustralian Centre for NanoMedicine, UNSW Sydney, Sydney, NSW, Australia.
Peter W GunningSchool of Biomedical Sciences, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-0833-3128
Edna C HardemanSchool of Biomedical Sciences, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-1649-7712
Amber JohnsAustralian Pancreatic Cancer Genome Initiative (APGI), Garvan Institute of Medical Research, Sydney, NSW, Australia.
Anthony J GillThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-9447-1967
Renee M WhanKatharina Gaus Light Microscopy Facility, Mark Wainwright Analytical Centre, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Amanda MawsonPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Omali PitiyarachchiPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Australian Pancreatic Cancer Genome Initiative
Joshua A McCarrollAustralian Centre for NanoMedicine, UNSW Sydney, Sydney, NSW, Australia.
Phoebe A PhillipsPancreatic Cancer Translational Research Group, School of Biomedical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia. p.phillips@unsw.edu.au.

Funding

Department of Health | National Health and Medical Research Council (NHMRC) APP1144108Department of Health | National Health and Medical Research Council (NHMRC) APP2002707
6 · The paper itself

Abstract

The microtubule protein βIII-tubulin is a prognostic, pro-survival, and chemoresistance factor in multiple malignancies, including pancreatic ductal adenocarcinoma (PDAC). However, the precise survival mechanisms controlled by βIII-tubulin in cancer remain unknown. Here, we discovered a link between βIII-tubulin and the activation of caspase 8-mediated extrinsic apoptosis. Silencing βIII-tubulin in PDAC cells activated caspase 8, leading to decreased cell viability and growth both in vitro and in vivo. βIII-tubulin knockdown also increased the sensitivity of PDAC cells to extrinsic cell death signals, including TNF-related apoptosis-inducing ligand (TRAIL), TNFα, and FasL. Furthermore, we demonstrated that βIII-tubulin knockdown in PDAC cells, in the absence or presence of TRAIL, increased diffusion and clustering of the TRAIL death receptor DR5 at the cell membrane, inducing extrinsic apoptosis. Nanoparticle delivery of βIII-tubulin siRNA to mouse PDAC tumours reduced tumour growth and increased responsiveness to TRAIL therapy. In patient-derived human PDAC explants, βIII-tubulin silencing reduced tumour cell frequency and improved sensitivity to TRAIL. Finally, we showed that high βIII-tubulin expression in the human PDAC stroma was independently prognostic for poor overall survival. Taken together, silencing βIII-tubulin represents an innovative strategy to activate a suicide signal in PDAC cells and render them more sensitive to microenvironment- and chemotherapy-derived death signals.

Indexed as

ApoptosisCarcinoma, Pancreatic DuctalPancreatic NeoplasmsTubulinAnimalsCaspase 8Cell Line, TumorFas Ligand ProteinHumansMiceReceptors, TNF-Related Apoptosis-Inducing LigandRNA, Small InterferingTNF-Related Apoptosis-Inducing LigandCaspase 8Fas Ligand ProteinReceptors, TNF-Related Apoptosis-Inducing LigandRNA, Small InterferingTNF-Related Apoptosis-Inducing LigandTUBB3 protein, humanTubulin

Identifiers

PMID42031726
PMCPMC13243481

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.