Evidence map›Paper›PMID 40157493›Full record

ArticleCancer letters2025

Glycosaminoglycan modification of NRP1 exon 4-skipping variant drives colorectal cancer metastasis via endosomal-exosomal trafficking.

Yiwei Gu, Qing Ye, Xiuping Huang, Yanan Cao, Luksana Chaiswing, Qing-Bai She

Abstract read
In one paragraph

Article in Cancer letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

6 authors.

Yiwei GuMarkey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, 40506, USA; Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, 40506, USA; Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Qing YeMarkey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, 40506, USA; Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, 40506, USA.
Xiuping HuangMarkey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, 40506, USA; Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, 40506, USA; Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Yanan CaoMarkey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, 40506, USA; Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, 40506, USA.
Luksana ChaiswingDepartment of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, Lexington, KY, 40506, USA.
Qing-Bai SheMarkey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, 40506, USA; Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, 40506, USA. Electronic address: qing-bai.she@uky.edu.

Funding

University of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI Bernard Mark Evers · 2013 to 2026
$38.3M
Targeting Translation Dependence in Colorectal Cancer ProgressionR01CA175105 · NCI · UNIVERSITY OF KENTUCKY · PI SHE, QING-BAI · 2013 to 2024
$3.3M
Natural product-based modulators of 4E-BP1 phosphorylationR01CA203257 · NCI · UNIVERSITY OF KENTUCKY · PI SHE, QING-BAI, THORSON, JON SCOTT · 2016 to 2020
$1.9M
Translational Control in Cr(VI) CarcinogenesisR21ES031712 · NIEHS · UNIVERSITY OF KENTUCKY · PI SHE, QING-BAI · 2020 to 2021
$421k
NCI NIH HHS P30 CA177558NCI NIH HHS R01 CA175105NCI NIH HHS R01 CA203257NIEHS NIH HHS R21 ES031712
6 · The paper itself

Abstract

Neuropilin-1 (NRP1) is a transmembrane glycoprotein that functions as a co-receptor with various cellular functions. Our previous studies identified the NRP1 exon 4-skipping (NRP1-ΔE4) splice variant as an aggressive metastasis driver by activating endosomal signals. Here, we demonstrate the critical role of glycosaminoglycan (GAG) modification in regulating NRP1-ΔE4's cellular trafficking and oncogenic activity. NRP1-ΔE4 undergoes constitutive internalization into endosomes and subsequent exosomal release from colorectal cancer (CRC) cells. Exosomal NRP1-ΔE4 enhances the migration and invasion of both donor and recipient CRC cells. Genetic or pharmacological inhibition of exosome secretion, or immunodepletion of exosomal NRP1-ΔE4, markedly reduces its metastatic potential. Notably, GAG modification at the O-glycosylation site Ser612 is essential for NRP1-ΔE4's endosomal trafficking and exosomal release. This modification also promotes the formation of a trimeric complex with Met and β1-integrin, leading to their co-internalization and accumulation in endosomes, which activates FAK signaling and drives CRC metastasis. These findings reveal GAG modification as a key regulatory process that governs the endosomal-exosomal trafficking of NRP1-ΔE4 to facilitate CRC cell dissemination.

Indexed as

Colorectal NeoplasmsEndosomesExosomesGlycosaminoglycansNeuropilin-1AnimalsCell Line, TumorCell MovementExonsHumansIntegrin beta1MiceNeoplasm MetastasisProtein TransportSignal TransductionGlycosaminoglycansIntegrin beta1Neuropilin-1NRP1 protein, humanColorectal cancerEndosomesExosomesGlycosaminoglycan modificationMetastasisNRP1NRP1-ΔE4

Identifiers

PMID40157493
PMCPMC12014352

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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.