Evidence map›Paper›PMID 38014454›Full record

ArticleThoracic cancer2024

The oncogenic role of LGR6 overexpression induced by aberrant Wnt/β-catenin signaling in lung cancer.

Noriaki Sunaga, Kyoichi Kaira, Kimihiro Shimizu, Ichidai Tanaka, Yosuke Miura, Seshiru Nakazawa, Yoichi Ohtaki, Reika Kawabata-Iwakawa, Mitsuo Sato, Luc Girard and 2 more

Open access · goldAbstract read
In one paragraph

Article in Thoracic cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Lgr6Genes & diseases · 2026
    Review
  3. Article
  4. Review
  5. Review
  6. Article
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 5 institutions in 2 countries.

Noriaki SunagaDepartment of Respiratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.ORCID 0000-0002-5966-4579
Kyoichi KairaDepartment of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Saitama, Japan.ORCID 0000-0001-5548-7686
Kimihiro ShimizuDivision of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, Nagano, Japan.
Ichidai TanakaDepartment of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yosuke MiuraDepartment of Respiratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
Seshiru NakazawaDivision of General Thoracic Surgery, Integrative Center of General Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan.
Yoichi OhtakiDivision of General Thoracic Surgery, Integrative Center of General Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan.ORCID 0000-0001-5485-3234
Reika Kawabata-IwakawaDivision of Integrated Oncology Research, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Japan.
Mitsuo SatoDivision of Host Defense Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Luc GirardHamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
John D MinnaHamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Takeshi HisadaGunma University Graduate School of Health Sciences, Maebashi, Japan.
Gunma University · JPNagoya University · JPThe University of Texas Southwestern Medical Center · USSaitama International Medical Center · JPShinshu University · JP

Funding

UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V. · 1996 to 2024
$57.4M
UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Kathryn Ann O'Donnell · 2010 to 2026
$53.7M
NCI NIH HHS P30 CA142543NCI NIH HHS P50 CA070907
6 · The paper itself

Abstract

backgroundMolecular abnormalities in the Wnt/β-catenin pathway confer malignant phenotypes in lung cancer. Previously, we identified the association of leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6) with oncogenic Wnt signaling, and its downregulation upon β-catenin knockdown in non-small cell lung cancer (NSCLC) cells carrying CTNNB1 mutations. The aim of this study was to explore the mechanisms underlying this association and the accompanying phenotypes.

methodsLGR6 expression in lung cancer cell lines and surgical specimens was analyzed using quantitative RT-PCR and immunohistochemistry. Cell growth was assessed using colony formation assay. Additionally, mRNA sequencing was performed to compare the expression profiles of cells subjected to different treatments.

resultsLGR6 was overexpressed in small cell lung cancer (SCLC) and NSCLC cell lines, including the CTNNB1-mutated NSCLC cell lines HCC15 and A427. In both cell lines, LGR6 knockdown inhibited cell growth. LGR6 expression was upregulated in spheroids compared to adherent cultures of A427 cells, suggesting that LGR6 participates in the acquisition of cancer stem cell properties. Immunohistochemical analysis of lung cancer specimens revealed that the LGR6 protein was predominantly overexpressed in SCLCs, large cell neuroendocrine carcinomas, and lung adenocarcinomas, wherein LGR6 overexpression was associated with vascular invasion, the wild-type EGFR genotype, and an unfavorable prognosis. Integrated mRNA sequencing analysis of HCC15 and A427 cells with or without LGR6 knockdown revealed LGR6-related pathways and genes associated with cancer development and stemness properties.

conclusionsOur findings highlight the oncogenic roles of LGR6 overexpression induced by aberrant Wnt/β-catenin signaling in lung cancer.

Indexed as

Carcinoma, Non-Small-Cell LungLung Neoplasmsbeta CateninCell Line, TumorCell ProliferationHumansReceptors, G-Protein-CoupledRNA, MessengerWnt Signaling Pathwaybeta CateninLGR6 protein, humanReceptors, G-Protein-CoupledRNA, Messengernon-small cell lung canceroncogenesmall cell lung cancerWnt pathwayβ-catenin

Identifiers

PMID38014454
PMCPMC10788478
OpenAlexW4389098140

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.