Evidence map›Paper›PMID 30188867›Full record

ArticleThe Journal of clinical investigation2018

Lysyl-tRNA synthetase-expressing colon spheroids induce M2 macrophage polarization to promote metastasis.

Seo Hee Nam, Doyeun Kim, Doohyung Lee, Hye-Mi Lee, Dae-Geun Song, Jae Woo Jung, Ji Eon Kim, Hye-Jin Kim, Nam Hoon Kwon, Eun-Kyeong Jo and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

29 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
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  4. Article
  5. Seryl-tRNA synthetase inhibits Wnt signaling and breast cancer progression and metastasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  6. Review
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  12. Review
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  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. The pLysRS-ApInternational journal of molecular sciences · 2021
    Review
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

12 authors at 3 institutions in 1 country.

Seo Hee NamInterdisciplinary Program in Genetic Engineering.
Doyeun KimMedicinal Bioconvergence Research Center, Seoul National University, Seoul, Republic of Korea.
Doohyung LeeDepartment of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, and.
Hye-Mi LeeDepartment of Microbiology, Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Dae-Geun SongDepartment of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, and.
Jae Woo JungInterdisciplinary Program in Genetic Engineering.
Ji Eon KimDepartment of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, and.
Hye-Jin KimDepartment of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, and.
Nam Hoon KwonMedicinal Bioconvergence Research Center, Seoul National University, Seoul, Republic of Korea.
Eun-Kyeong JoDepartment of Microbiology, Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Sunghoon KimInterdisciplinary Program in Genetic Engineering.
Jung Weon LeeInterdisciplinary Program in Genetic Engineering.
Seoul National University · KRChungnam National University · KRKorea Institute of Science and Technology · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lysyl-tRNA synthetase (KRS) functions canonically in cytosolic translational processes. However, KRS is highly expressed in colon cancer, and localizes to distinct cellular compartments upon phosphorylations (i.e., the plasma membranes after T52 phosphorylation and the nucleus after S207 phosphorylation), leading to probably alternative noncanonical functions. It is unknown how other subcellular KRSs crosstalk with environmental cues during cancer progression. Here, we demonstrate that the KRS-dependent metastatic behavior of colon cancer spheroids within 3D gels requires communication between cellular molecules and extracellular soluble factors and neighboring cells. Membranous KRS and nuclear KRS were found to participate in invasive cell dissemination of colon cancer spheroids in 3D gels. Cancer spheroids secreted GAS6 via a KRS-dependent mechanism and caused the M2 polarization of macrophages, which activated the neighboring cells via secretion of FGF2/GROα/M-CSF to promote cancer dissemination under environmental remodeling via fibroblast-mediated laminin production. Analyses of tissues from clinical colon cancer patients and Krs-/+ animal models for cancer metastasis supported the roles of KRS, GAS6, and M2 macrophages in KRS-dependent positive feedback between tumors and environmental factors. Altogether, KRS in colon cancer cells remodels the microenvironment to promote metastasis, which can thus be therapeutically targeted at these bidirectional KRS-dependent communications of cancer spheroids with environmental cues.

Indexed as

Gene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticTumor MicroenvironmentAnimalsChemokine CXCL1Colonic NeoplasmsFibroblast Growth Factor 2FibroblastsGrowth Arrest-Specific Protein 6HCT116 CellsHumansIntercellular Signaling Peptides and ProteinsLysine-tRNA LigaseMacrophagesMiceMice, Inbred BALB CChemokine CXCL1CXCL1 protein, humanFibroblast Growth Factor 2Growth Arrest-Specific Protein 6Intercellular Signaling Peptides and ProteinsKARS1 protein, humanLysine-tRNA LigaseNeoplasm ProteinsCancerCell migration/adhesionGastroenterologyMacrophagesOncology

Identifiers

PMID30188867
PMCPMC6205414
OpenAlexW2892045569

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.