Evidence map›Paper›PMID 29695769›Full record

ArticleBritish journal of cancer2018

Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition.

Dae Joong Kim, James M Dunleavey, Lin Xiao, David W Ollila, Melissa A Troester, Carol A Otey, Wei Li, Thomas H Barker, Andrew C Dudley

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

Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

42 citing papers in PubMed, 73 citations in OpenAlex.

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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

9 authors at 4 institutions in 2 countries.

Dae Joong KimDepartment of Microbiology, Immunology, and Cancer Biology, The University of Virginia, Charlottesville, VA, 22908, USA.
James M DunleaveyNational Cancer Institute, Tumor Angiogenesis Unit, Center for Cancer Research, Frederick, MD, 21702, USA.
Lin XiaoChildren's Cancer Institute, Kensington, NSW 2750, Australia.
David W OllilaDepartment of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Melissa A TroesterGillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Carol A OteyDepartment of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Wei LiDepartment of Biomedical Engineering, The University of Virginia, Charlottesville, VA, 22908, USA.
Thomas H BarkerDepartment of Biomedical Engineering, The University of Virginia, Charlottesville, VA, 22908, USA.
Andrew C DudleyDepartment of Microbiology, Immunology, and Cancer Biology, The University of Virginia, Charlottesville, VA, 22908, USA. acd2g@virginia.edu.
University of Virginia · USUniversity of North Carolina at Chapel Hill · USCenter for Cancer Research · USChildren's Cancer Institute Australia · AU

Funding

Targeting the vasculature to enhance anti-tumor immunityR01CA177875 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Andrew Carl Dudley · 2014 to 2026
$4.5M
NCI NIH HHS R01 CA177875
6 · The paper itself

Abstract

backgroundCancer-associated fibroblasts (CAFs) support tumour progression and invasion, and they secrete abundant extracellular matrix (ECM) that may shield tumour cells from immune checkpoint or kinase inhibitors. Targeting CAFs using drugs that revert their differentiation, or inhibit their tumour-supportive functions, has been considered as an anti-cancer strategy.

methodsWe have used human and murine cell culture models, atomic force microscopy (AFM), microarray analyses, CAF/tumour cell spheroid co-cultures and transgenic fibroblast reporter mice to study how targeting HDACs using small molecule inhibitors or siRNAs re-directs CAF differentiation and function in vitro and in vivo.

resultsFrom a small molecule screen, we identified Scriptaid, a selective inhibitor of HDACs 1/3/8, as a repressor of TGFβ-mediated CAF differentiation. Scriptaid inhibits ECM secretion, reduces cellular contraction and stiffness, and impairs collective cell invasion in CAF/tumour cell spheroid co-cultures. Scriptaid also reduces CAF abundance and delays tumour growth in vivo.

conclusionsScriptaid is a well-tolerated and effective HDACi that reverses many of the functional and phenotypic properties of CAFs. Impeding or reversing CAF activation/function by altering the cellular epigenetic regulatory machinery could control tumour growth and invasion, and be beneficial in combination with additional therapies that target cancer cells or immune cells directly.

Indexed as

AnimalsCancer-Associated FibroblastsCell DifferentiationCell Line, TumorCell MovementCoculture TechniquesEndothelial CellsExtracellular MatrixFibroblastsHistone Deacetylase InhibitorsHumansHydroxylaminesMiceMicroarray AnalysisMicroscopy, Atomic ForceNeoplasmsHistone Deacetylase InhibitorsHydroxylaminesQuinolinesscriptaidTransforming Growth Factor beta

Identifiers

PMID29695769
PMCPMC5959903
OpenAlexW2800978766

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.