Evidence map›Paper›PMID 20038581›Full record

ArticleThe Journal of biological chemistry2010

Constitutively active inflammasome in human melanoma cells mediating autoinflammation via caspase-1 processing and secretion of interleukin-1beta.

Miyako Okamoto, Weimin Liu, Yuchun Luo, Aki Tanaka, Xiangna Cai, David A Norris, Charles A Dinarello, Mayumi Fujita

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers.

0numbers the graph read from it
0cells of the map it votes in
188citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

188 citing papers in PubMed, 292 citations in OpenAlex.

  1. Blocking IL-1β reverses the immunosuppression in mouse breast cancer and synergizes with anti-PD-1 for tumor abrogation.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Trial
  2. Trial
  3. Interleukin-1β Gene (Current oncology (Toronto, Ont.) · 2026
    Article
  4. Review
  5. Observational
  6. De novo discovery of bicyclic cysteine-rich peptides targeting gasdermin D.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Observational
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Therapeutic Significance of NLRP3 Inflammasome in Cancer: Friend or Foe?International journal of molecular sciences · 2024
    Review
  18. Article
  19. The Role of Caspases in Melanoma Pathogenesis.Current issues in molecular biology · 2024
    Review
  20. Article

128 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

8 authors at 1 institution in 1 country.

Miyako OkamotoDepartment of Dermatology, University of Colorado Denver, Aurora, Colorado 80045, USA.
Weimin Liu
Yuchun Luo
Aki Tanaka
Xiangna Cai
David A Norris
Charles A Dinarello
Mayumi Fujita
University of Colorado Denver · US

Funding

Yeast-based HTS Assay Technologies for ProteasesR01AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1985 to 2025
$8.5M
Training in Translational Research of Skin DiseasesT32AR007411 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI ASGARI, MARYAM MANDANA, ROOP, DENNIS · 1986 to 2025
$4.8M
Pathogenesis of Fever in ManR56AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 2016 to 2016
$311k
Developing a protocol for profiling blood markers of melanomaR03CA125833 · NCI · UNIVERSITY OF COLORADO DENVER · PI FUJITA, MAYUMI · 2008 to 2009
$154k
PATHOGENESIS OF FEVER IN HUMANSR37AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1988 to 1998
–
NCI NIH HHS CA125833NCI NIH HHS R03 CA125833NIAID NIH HHS AI-15614NIAID NIH HHS R01 AI015614NIAID NIH HHS R56 AI015614NIAMS NIH HHS 5T32AR007411NIAMS NIH HHS T32 AR007411
6 · The paper itself

Abstract

Interleukin-1beta (IL-1beta) is a pleiotropic cytokine promoting inflammation, angiogenesis, and tissue remodeling as well as regulation of immune responses. Although IL-1beta contributes to growth and metastatic spread in experimental and human cancers, the molecular mechanisms regulating the conversion of the inactive IL-1beta precursor to a secreted and active cytokine remains unclear. Here we demonstrate that NALP3 inflammasome is constitutively assembled and activated with cleavage of caspase-1 in human melanoma cells. Late stage human melanoma cells spontaneously secrete active IL-1beta via constitutive activation of the NALP3 inflammasome and IL-1 receptor signaling, exhibiting a feature of autoinflammatory diseases. Unlike human blood monocytes, these melanoma cells require no exogenous stimulation. In contrast, NALP3 functionality in intermediate stage melanoma cells requires activation of the IL-1 receptor to secrete active IL-1beta; cells from an early stage of melanoma require stimulation of the IL-1 receptor plus the co-stimulant muramyl dipeptide. The spontaneous secretion of IL-1beta from melanoma cells was reduced by inhibition of caspase-1 or the use of small interfering RNA directed against ASC. Supernatants from melanoma cell cultures enhanced macrophage chemotaxis and promoted in vitro angiogenesis, both prevented by pretreating melanoma cells with inhibitors of caspases-1 and -5 or IL-1 receptor blockade. These findings implicate IL-1-mediated autoinflammation as contributing to the development and progression of human melanoma and suggest that inhibiting the inflammasome pathway or reducing IL-1 activity can be a therapeutic option for melanoma patients.

Indexed as

Carrier ProteinsCaspase 2Cell Line, TumorChemotaxisHumansInflammationInterleukin-1betaMacrophagesMelanomaNeovascularization, PathologicNLR Family, Pyrin Domain-Containing 3 ProteinReceptors, Interleukin-1Carrier ProteinsCaspase 2Interleukin-1betaNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanReceptors, Interleukin-1

Identifiers

PMID20038581
PMCPMC2825443
OpenAlexW2064672822

What OpenQuestion holds

Textmetadata
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.