Evidence map›Paper›PMID 35326747›Full record

ArticleCancers2022

Selective Targeting of Protein Kinase C (PKC)-θ Nuclear Translocation Reduces Mesenchymal Gene Signatures and Reinvigorates Dysfunctional CD8

Jenny Dunn, Robert D McCuaig, Abel H Y Tan, Wen Juan Tu, Fan Wu, Kylie M Wagstaff, Anjum Zafar, Sayed Ali, Himanshu Diwakar, Jane E Dahlstrom and 15 more

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

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 21% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
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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

25 authors at 10 institutions in 1 country.

Jenny DunnGene Regulation and Translational Medicine Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
Robert D McCuaigGene Regulation and Translational Medicine Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
Abel H Y TanMelanie Swan Memorial Translational Centre, Faculty of Science and Technology, University of Canberra, Canberra, ACT 2617, Australia.
Wen Juan TuGene Regulation and Translational Medicine Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
Fan WuMelanie Swan Memorial Translational Centre, Faculty of Science and Technology, University of Canberra, Canberra, ACT 2617, Australia.ORCID 0000-0001-7763-8852
Kylie M WagstaffCancer Targeting and Nuclear Therapeutics Lab, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia.
Anjum ZafarMelanie Swan Memorial Translational Centre, Faculty of Science and Technology, University of Canberra, Canberra, ACT 2617, Australia.
Sayed AliMedical Oncology, St John of God Midland Public and Private Hospitals, Perth, WA 6056, Australia.
Himanshu DiwakarWoden Specialist Medical Centre, I-MED Radiology Network, Canberra, ACT 2606, Australia.
Jane E DahlstromAnatomical Pathology, ACT Pathology, The Canberra Hospital, Canberra Health Services, Canberra, ACT 2605, Australia.ORCID 0000-0001-5608-693X
Elaine G BeanAnatomical Pathology, ACT Pathology, The Canberra Hospital, Canberra Health Services, Canberra, ACT 2605, Australia.
Jade K ForwoodSchool of Dentistry and Medical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
Sofiya TsimbalyukSchool of Dentistry and Medical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
Emily M CrossSchool of Dentistry and Medical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
Kristine HardyMelanie Swan Memorial Translational Centre, Faculty of Science and Technology, University of Canberra, Canberra, ACT 2617, Australia.
Amanda L BainGene Regulation and Translational Medicine Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
Elizabeth AhernDepartment of Medical Oncology, Monash Health and Monash University, Melbourne, VIC 3168, Australia.
Riccardo DolcettiPeter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
Roberta MazzieriPeter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
Desmond YipANU Medical School, College of Health and Medicine, The Australian National University, Canberra, ACT 0200, Australia.ORCID 0000-0002-2806-2401
Melissa EastgateDepartment of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia.
Laeeq MalikANU Medical School, College of Health and Medicine, The Australian National University, Canberra, ACT 0200, Australia.
Peter MilburnThe John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia.
David A JansNuclear Signaling Lab, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia.ORCID 0000-0001-5115-4745
Sudha RaoGene Regulation and Translational Medicine Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.ORCID 0000-0001-9547-947X
University of Canberra · AUAustralian National University · AUCharles Sturt University · AUQIMR Berghofer Medical Research Institute · AUTranslational Research Institute · AUAustralian Regenerative Medicine Institute · AUCanberra Hospital · AUMonash University · AUSt John of God Hospital · AUThe University of Queensland · AU

Funding

National Health and Medical Research Council GNT1105409
6 · The paper itself

Abstract

Protein kinase C (PKC)-θ is a serine/threonine kinase with both cytoplasmic and nuclear functions. Nuclear chromatin-associated PKC-θ (nPKC-θ) is increasingly recognized to be pathogenic in cancer, whereas its cytoplasmic signaling is restricted to normal T-cell function. Here we show that nPKC-θ is enriched in circulating tumor cells (CTCs) in patients with triple-negative breast cancer (TNBC) brain metastases and immunotherapy-resistant metastatic melanoma and is associated with poor survival in immunotherapy-resistant disease. To target nPKC-θ, we designed a novel PKC-θ peptide inhibitor (nPKC-θi2) that selectively inhibits nPKC-θ nuclear translocation but not PKC-θ signaling in healthy T cells. Targeting nPKC-θ reduced mesenchymal cancer stem cell signatures in immunotherapy-resistant CTCs and TNBC xenografts. PKC-θ was also enriched in the nuclei of CD8

Indexed as

breast cancercancer stem cellepithelial-to-mesenchymal transitionimmunotherapymelanomametastasisnuclear translocationprotein kinase C (PKC)-θresistanceT cell

Identifiers

PMID35326747
PMCPMC8946217
OpenAlexW4220690019

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.