Evidence map›Paper›PMID 39438124›Full record

ArticleGut2025

IQGAP3 signalling mediates intratumoral functional heterogeneity to enhance malignant growth.

Mitsuhiro Shimura, Junichi Matsuo, ShuChin Pang, Nawaphat Jangphattananont, Aashiq Hussain, Muhammad Bakhait Rahmat, Jung-Won Lee, Daisuke Douchi, Jasmine Jie Lin Tong, Khine Myint and 10 more

Abstract read
In one paragraph

Article in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

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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.

Mitsuhiro ShimuraCancer Science Institute of Singapore, National University of Singapore, Singapore.
Junichi MatsuoCancer Science Institute of Singapore, National University of Singapore, Singapore.ORCID 0000-0002-2378-2370
ShuChin PangCancer Science Institute of Singapore, National University of Singapore, Singapore.
Nawaphat JangphattananontCancer Science Institute of Singapore, National University of Singapore, Singapore.
Aashiq HussainCancer Science Institute of Singapore, National University of Singapore, Singapore.
Muhammad Bakhait RahmatCancer Science Institute of Singapore, National University of Singapore, Singapore.
Jung-Won LeeCancer Science Institute of Singapore, National University of Singapore, Singapore.
Daisuke DouchiCancer Science Institute of Singapore, National University of Singapore, Singapore.ORCID 0000-0003-4582-6589
Jasmine Jie Lin TongCancer Science Institute of Singapore, National University of Singapore, Singapore.
Khine MyintCancer Science Institute of Singapore, National University of Singapore, Singapore.
Supriya SrivastavaDepartment of Medicine, National University of Singapore, Singapore.
Ming TehDepartment of Medicine, National University of Singapore, Singapore.
Vivien KohCancer Science Institute of Singapore, National University of Singapore, Singapore.
Wei Peng YongCancer Science Institute of Singapore, National University of Singapore, Singapore.
Jimmy Bok Yan SoDepartment of Surgery, National University of Singapore, Singapore.
Patrick TanCancer Science Institute of Singapore, National University of Singapore, Singapore.ORCID 0000-0002-0179-8048
Khay-Guan YeohDepartment of Medicine, National University of Singapore, Singapore.ORCID 0000-0002-7802-4606
Michiaki UnnoDepartment of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Linda Shyue Huey ChuangCancer Science Institute of Singapore, National University of Singapore, Singapore csiitoy@nus.edu.sg csicshl@nus.edu.sg.ORCID 0000-0001-9078-9532
Yoshiaki ItoCancer Science Institute of Singapore, National University of Singapore, Singapore csiitoy@nus.edu.sg csicshl@nus.edu.sg.ORCID 0000-0002-9037-1184

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe elevation of IQGAP3 expression in diverse cancers indicates a key role for IQGAP3 in carcinogenesis. Although IQGAP3 was established as a proliferating stomach stem cell factor and a regulator of the RAS-ERK pathway, how it drives cancer growth remains unclear.

objectiveWe define the function of IQGAP3 in gastric cancer (GC) development and progression.

designWe studied the phenotypic changes caused by IQGAP3 knockdown in three molecularly diverse GC cell lines by RNA-sequencing. In vivo tumorigenesis and lung metastasis assays corroborated IQGAP3 as a mediator of oncogenic signalling. Spatial analysis was performed to evaluate the intratumoral transcriptional and functional differences between control tumours and IQGAP3 knockdown tumours.

resultsTranscriptomic profiling showed that IQGAP3 inhibition attenuates signal transduction networks, such as KRAS signalling, via phosphorylation blockade. IQGAP3 knockdown was associated with significant inhibition of MEK/ERK signalling-associated growth factors, including TGFβ1, concomitant with gene signatures predictive of impaired tumour microenvironment formation and reduced metastatic potential. Xenografts involving IQGAP3 knockdown cells showed attenuated tumorigenesis and lung metastasis in immunodeficient mice. Accordingly, immunofluorescence staining revealed significant reductions of TGFβ/SMAD signalling and αSMA-positive stromal cells; digital spatial analysis indicated that IQGAP3 is indispensable for the formation of two phenotypically diverse cell subpopulations, which played crucial but distinct roles in promoting oncogenic functions.

conclusionIQGAP3 knockdown suppressed the RAS-TGFβ signalling crosstalk, leading to a significant reduction of the tumour microenvironment. In particular, IQGAP3 maintains functional heterogeneity of cancer cells to enhance malignant growth. IQGAP3 is thus a highly relevant therapy target in GC.

Indexed as

GTPase-Activating Proteinsras GTPase-Activating ProteinsStomach NeoplasmsAnimalsCarcinogenesisCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansLung NeoplasmsMiceSignal TransductionTumor MicroenvironmentGTPase-Activating ProteinsIQGAP3 protein, humanras GTPase-Activating Proteinscarcinogenesissignal transduction

Identifiers

PMID39438124
PMCPMC11874294

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.