Evidence map›Paper›PMID 41981140›Full record

ArticleBritish journal of cancer2026

Notch signaling governs colorectal cancer metastasis via transcriptional control of TGF-β effectors SMAD2/SMAD3.

Yaochun Wang, Jingzhuo Song, Shaoran Song, Shuhang Zheng, Yuyao Li, Lingxiao Zhang, Shuhong Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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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

1 citing paper in PubMed.

  1. Article
4 · The record

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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

7 authors.

Yaochun Wang *Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P. R. China.
Jingzhuo Song *Department of Oncology, Xi 'an Chang 'an District Hospital, Xi'an, Shaanxi Province, P. R. China.
Shaoran Song *Department of Radiotherapy, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Shuhang ZhengDepartment of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P. R. China.
Yuyao LiDepartment of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University (Yulin Hospital), Yulin, Shaanxi Province, P. R. China.
Lingxiao ZhangDepartment of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P. R. China.
Shuhong WangDepartment of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P. R. China. wangsh@xjtufh.edu.cn.ORCID http://orcid.org/0000-0001-7624-478X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe molecular interplay between Notch and TGF-β signaling in colorectal cancer (CRC) metastasis remains poorly understood.

methodsGenetic ablation of RBP-J, the central transcriptional mediator of Notch signaling, was performed in CRC cells. In vitro functional assays assessed migration, invasion, and transendothelial migration. Metastatic colonization was evaluated in vivo using orthotopic, intrasplenic, and intravenous murine models. Whole-transcriptome analysis, chromatin immunoprecipitation sequencing (ChIP-seq), and luciferase reporter assays were used to analyze RBP-J-mediated transcriptional regulation of SMAD2/SMAD3. Rescue experiments reconstituted SMAD2/SMAD3 in RBP-J knockout (KO) cells to verify functional necessity.

resultsRBP-J knockout profoundly impaired CRC cell migration, invasion, and transendothelial migration in vitro, and suppressed metastatic colonization across multiple in vivo models. Transcriptomic and ChIP-seq analyses revealed RBP-J directly binds to SMAD2 and SMAD3 promoters and activates their transcription. Reconstitution of SMAD2/SMAD3 restored the migratory and metastatic capacities of RBP-J KO cells. Mechanistically, Notch signaling primes TGF-β responsiveness by maintaining SMAD2/SMAD3 expression and phosphorylation, establishing a feedforward loop essential for metastasis.

conclusionNotch signaling orchestrates TGF-β-driven metastasis through direct transcriptional control of SMAD2/SMAD3, defining a hierarchical regulatory axis. This offers novel therapeutic targets for metastatic CRC.

Indexed as

Colorectal NeoplasmsReceptors, NotchSmad2 ProteinSmad3 ProteinTransforming Growth Factor betaAnimalsCell Line, TumorCell MovementGene Expression Regulation, NeoplasticHumansImmunoglobulin J Recombination Signal Sequence-Binding ProteinMiceNeoplasm InvasivenessNeoplasm MetastasisSignal TransductionTranscription, GeneticImmunoglobulin J Recombination Signal Sequence-Binding ProteinRbpj protein, mouseReceptors, NotchSmad2 ProteinSMAD2 protein, humanSmad3 ProteinSMAD3 protein, humanTransforming Growth Factor beta

Identifiers

PMID41981140
PMCPMC13269697

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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.