Evidence map›Paper›PMID 31110180›Full record

ArticleNature communications2019

LNK suppresses interferon signaling in melanoma.

Ling-Wen Ding, Qiao-Yang Sun, Jarem J Edwards, Lucia Torres Fernández, Xue-Bin Ran, Si-Qin Zhou, Richard A Scolyer, James S Wilmott, John F Thompson, Ngan Doan and 10 more

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

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. Lnk Governs chemokine-directed trafficking of CD8Molecular therapy. Oncology · 2026
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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

20 authors at 5 institutions in 3 countries.

Ling-Wen DingCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Qiao-Yang SunCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore. qiaoyangsun@gmail.com.ORCID http://orcid.org/0000-0002-9855-5586
Jarem J EdwardsMelanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
Lucia Torres FernándezCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Xue-Bin RanCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Si-Qin ZhouCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Richard A ScolyerMelanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.ORCID http://orcid.org/0000-0002-8991-0013
James S WilmottMelanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
John F ThompsonMelanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
Ngan DoanSanta Monica-University of California, Los Angeles Medical Center, Los Angeles, CA, 90095, USA.
Jonathan W SaidSanta Monica-University of California, Los Angeles Medical Center, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0001-9474-2563
Nachiyappan VenkatachalamCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.ORCID http://orcid.org/0000-0003-4293-8278
Jin-Fen XiaoCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Xin-Yi LohCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Maren PeinCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Liang XuCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
David W MullinsDepartments of Medical Education and Microbiology/Immunology, Geisel School of Medicine at Dartmouth, Dartmouth, MA, 03755, USA.ORCID http://orcid.org/0000-0002-2644-350X
Henry YangCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
De-Chen LinDivision of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, 90048, USA.
H Phillip KoefflerCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.ORCID http://orcid.org/0000-0001-5839-9913
National University of Singapore · SGThe University of Sydney · AUCedars-Sinai Medical Center · USUniversity of California, Los Angeles · USDartmouth College · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

LNK (SH2B3) is a key negative regulator of JAK-STAT signaling which has been extensively studied in malignant hematopoietic diseases. We found that LNK is significantly elevated in cutaneous melanoma; this elevation is correlated with hyperactive signaling of the RAS-RAF-MEK pathway. Elevated LNK enhances cell growth and survival in adverse conditions. Forced expression of LNK inhibits signaling by interferon-STAT1 and suppresses interferon (IFN) induced cell cycle arrest and cell apoptosis. In contrast, silencing LNK expression by either shRNA or CRISPR-Cas9 potentiates the killing effect of IFN. The IFN-LNK signaling is tightly regulated by a negative feedback mechanism; melanoma cells exposed to IFN upregulate expression of LNK to prevent overactivation of this signaling pathway. Our study reveals an unappreciated function of LNK in melanoma and highlights the critical role of the IFN-STAT1-LNK signaling axis in this potentially devastating disease. LNK may be further explored as a potential therapeutic target for melanoma immunotherapy.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsApoptosisCell Cycle CheckpointsCell Line, TumorHEK293 CellsHumansInterferonsIntracellular Signaling Peptides and ProteinsMelanomaMembrane ProteinsMiceMice, Inbred C57BLMice, Inbred NODMice, SCIDProteinsAdaptor Proteins, Signal TransducingInterferonsIntracellular Signaling Peptides and ProteinsLnk protein, mouseMembrane ProteinsProteinsSH2B3 protein, humanSTAT1 protein, humanStat1 protein, mouseSTAT1 Transcription Factor

Identifiers

PMID31110180
PMCPMC6527565
OpenAlexW2946507587

What Socratic 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 Socratic graph.