Evidence map›Paper›PMID 32291710›Full record

ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2020

Uptake and tumor-suppressive pathways of exosome-associated GKN1 protein in gastric epithelial cells.

Jung Hwan Yoon, Hassan Ashktorab, Duane T Smoot, Suk Woo Nam, Hoon Hur, Won Sang Park

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

32 citing papers in PubMed, 38 citations in OpenAlex.

  1. Biology and Therapeutic Potential of Exosomes, Targeted Drug Delivery.International journal of molecular sciences · 2026
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  13. Therapeutic Applications of Stem Cell-Derived Exosomes.International journal of molecular sciences · 2024
    Review
  14. The biological role of extracellular vesicles in gastric cancer metastasis.Frontiers in cell and developmental biology · 2024
    Review
  15. Circulating Proteins as Diagnostic Markers in Gastric Cancer.International journal of molecular sciences · 2023
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  16. Article
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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

6 authors at 4 institutions in 2 countries.

Jung Hwan YoonDepartment of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, South Korea.
Hassan AshktorabDepartment of Medicine, Howard University, District of Columbia, Washington, 20060, USA.
Duane T SmootDepartment of Medicine, Meharry Medical Center, Nashville, TN, 37208, USA.
Suk Woo NamDepartment of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, South Korea.
Hoon HurDepartment of Surgery, Brain Korea 21 Plus Research Center for Biomedical Science, Ajou University School of Medicine, Suwon, 16499, South Korea.
Won Sang ParkDepartment of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, South Korea. wonsang@catholic.ac.kr.ORCID 0000-0002-9090-0584
Catholic University of Korea · KRAjou University · KRHoward University · USMeharry Medical College · US

Funding

National Research Foundation of Korea 2018R1A2A2A14019713
6 · The paper itself

Abstract

backgroundGastrokine 1 (GKN1) is a stomach-specific tumor suppressor that is secreted into extracellular space as an exosomal cargo protein. The objective of this study was to investigate the uptake and tumor-suppressive pathways of exosome-associated GKN1 protein in gastric epithelial cells.

methodsImmunofluorescent and Western blot analysis were used to investigate gastric-specific uptake of HFE-145-derived exosomes. Binding affinity of HFE-145 derived exosomes with integrin proteins was examined using protein microarray chip. Tumor suppressor activities of exosome-carrying GKN1 protein were analyzed using transwell co-culture, MTT assay, BrdU incorporation, immunoprecipitation, and Western blot analysis.

resultsHFE-145-derived exosomes were internalized only into HFE-145 gastric epithelial cells and gastric cancer cells. Gastric-specific uptake of stomach-derived exosomes required integrin α6 and αX proteins. Clathrin and macropinocytosis increased the uptake of exosomes into gastric epithelial cells, whereas caveolin inhibited the uptake of exosomes. Transwell co-culture of AGS cells with HFE-145 cells markedly inhibited viability and proliferation of AGS cells. Following uptake of HFE-145-derived exosomes in recipient cells, GKN1 protein bound to HRas and inhibited the binding of HRas to b-Raf and c-Raf which subsequently downregulated HRas/Raf/MEK/ERK signaling pathways in AGS, MKN1 cells, and MKN1-derived xenograft tumor tissues. In addition, exosomal GKN1 protein suppressed both migration and invasion of gastric cancer cells by inhibiting epithelial-mesenchymal transition.

conclusionsGastric-specific uptake of exosomes derived from gastric epithelial cells requires integrin α6 and αX proteins in both gastric epithelial cells and exosomes. Exosomal GKN1 protein inhibits gastric carcinogenesis by downregulating HRas/Raf/MEK/ERK signaling pathways.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsApoptosisCell ProliferationEpithelial CellsEpithelial-Mesenchymal TransitionExosomesHumansIntegrinsMicePeptide HormonesPinocytosisStomachStomach NeoplasmsTumor Cells, CulturedTumor Suppressor ProteinsGKN1 protein, humanIntegrinsPeptide HormonesTumor Suppressor ProteinsExosomeGastric cancerGKN1Ras signalingUptake

Identifiers

PMID32291710
OpenAlexW3016169869

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.