Evidence map›Paper›PMID 35365657›Full record

ArticleNature communications2022

PI3Kγ stimulates a high molecular weight form of myosin light chain kinase to promote myeloid cell adhesion and tumor inflammation.

Michael C Schmid, Sang Won Kang, Hui Chen, Marc Paradise, Anghesom Ghebremedhin, Megan M Kaneda, Shao-Ming Chin, Anh Do, D Martin Watterson, Judith A Varner

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Trial
  2. Review
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  4. Review
  5. One Step Ahead: Preventing Tumor Adaptation to Immune Therapy.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2025
    Review
  6. Targeting PI3Kγ in cancer.Trends in cancer · 2025
    Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
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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

10 authors at 4 institutions in 3 countries.

Michael C SchmidMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA. M.Schmid@liverpool.ac.uk.
Sang Won KangDepartment of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea.
Hui ChenMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Marc ParadiseMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Anghesom GhebremedhinMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Megan M KanedaMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Shao-Ming ChinMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Anh DoMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
D Martin WattersonDepartment of Pharmacology, Northwestern University, Chicago, IL, USA.
Judith A VarnerMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA. jvarner@health.ucsd.edu.ORCID http://orcid.org/0000-0002-9251-0600
University of California San Diego · USEwha Womans University · KRNorthwestern University · USUC San Diego Health System · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
Role of PI3Kinase in Tumor Progression and MetastasisR01CA167426 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Judith A VARNER · 2012 to 2026
$5.8M
Targeting the innate immune response in HNSCCR01DE027325 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Judith A VARNER · 2017 to 2026
$4.8M
Therapeutic Targeting of Macrophage PI3Kgamma in HNSCCR01CA226909 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kathryn Ann Gold, Judith A VARNER · 2018 to 2026
$3.9M
NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA167426NCI NIH HHS R01 CA226909NIDCR NIH HHS R01 DE027325
6 · The paper itself

Abstract

Myeloid cells play key roles in cancer immune suppression and tumor progression. In response to tumor derived factors, circulating monocytes and granulocytes extravasate into the tumor parenchyma where they stimulate angiogenesis, immune suppression and tumor progression. Chemokines, cytokines and interleukins stimulate PI3Kγ-mediated Rap1 activation, leading to conformational changes in integrin α4β1 that promote myeloid cell extravasation and tumor inflammation Here we show that PI3Kγ activates a high molecular weight form of myosin light chain kinase, MLCK210, that promotes myosin-dependent Rap1 GTP loading, leading to integrin α4β1 activation. Genetic or pharmacological inhibition of MLCK210 suppresses integrin α4β1 activation, as well as tumor inflammation and progression. These results demonstrate a critical role for myeloid cell MLCK210 in tumor inflammation and serve as basis for the development of alternative approaches to develop immune oncology therapeutics.

Indexed as

Myosin-Light-Chain KinaseNeoplasmsCell AdhesionClass Ib Phosphatidylinositol 3-KinaseHumansInflammationMolecular WeightMyeloid CellsClass Ib Phosphatidylinositol 3-KinaseMyosin-Light-Chain KinasePIK3CG protein, human

Identifiers

PMID35365657
PMCPMC8975949
OpenAlexW4220808500

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.