Evidence map›Paper›PMID 35661943›Full record

ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2022

Potential therapeutic targets discovery by transcriptome analysis of an in vitro human gastric signet ring carcinoma model.

Kyoko Yamaguchi, Tomoyasu Yoshihiro, Hiroshi Ariyama, Mamoru Ito, Michitaka Nakano, Yuichiro Semba, Jumpei Nogami, Kenji Tsuchihashi, Takuji Yamauchi, Shohei Ueno and 18 more

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Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 29% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

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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

28 authors at 4 institutions in 1 country.

Kyoko YamaguchiDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Tomoyasu YoshihiroDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Hiroshi AriyamaDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. ariyama.hiroshi.915@m.kyushu-u.ac.jp.ORCID 0000-0002-8374-5045
Mamoru ItoDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Michitaka NakanoDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Yuichiro SembaDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Jumpei NogamiDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Kenji TsuchihashiDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Takuji YamauchiDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Shohei UenoDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Taichi IsobeDepartment of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Koji ShindoDepartment of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Taiki MoriyamaDepartment of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kenoki OhuchidaDepartment of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Masafumi NakamuraDepartment of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yoshihiro NagaoDepartment of Advanced Medicine and Innovative Technology, Kyushu University Hospital, Fukuoka, Japan.
Tetsuo IkedaDepartment of Advanced Medicine and Innovative Technology, Kyushu University Hospital, Fukuoka, Japan.
Makoto HashizumeDepartment of Advanced Medicine and Innovative Technology, Kyushu University Hospital, Fukuoka, Japan.
Hiroyuki KonomiDepartment of Surgery, Hamanomachi Hospital, Fukuoka, Japan.
Takehiro TorisuDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takanari KitazonoDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Tomohiro KanayamaDepartment of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu, Japan.
Hiroyuki TomitaDepartment of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu, Japan.
Yoshinao OdaDepartment of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hitoshi KusabaDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Takahiro MaedaDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Koichi AkashiDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Eishi BabaDepartment of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kyushu University · JPGifu University · JPKyushu University Hospital · JPHamanomachi Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLoss of E-cadherin expression is frequently observed in signet ring carcinoma (SRCC). People with germline mutations in CDH1, which encodes E-cadherin, develop diffuse gastric cancer at a higher rate. Loss of E-cadherin expression is thus assumed to trigger oncogenic development.

methodsTo investigate novel therapeutic targets for gastric SRCC, we engineered an E-cadherin-deficient SRCC model in vitro using a human gastric organoid (hGO) with CDH1 knockout (KO).

resultsCDH1 KO hGO cells demonstrated distinctive morphological changes similar to SRCC and high cell motility. RNA-sequencing revealed up-regulation of matrix metalloproteinase (MMP) genes in CDH1 KO hGO cells compared to wild type. MMP inhibitors suppressed cell motility of CDH1 KO hGO cells and SRCC cell lines in vitro. Immunofluorescent analysis with 95 clinical gastric cancer tissues revealed that MMP-3 was specifically abundant in E-cadherin-aberrant SRCC. In addition, CXCR4 molecules translocated onto the cell membrane after CDH1 KO. Addition of CXCL12, a ligand of CXCR4, to the culture medium prolonged cell survival of CDH1 KO hGO cells and was abolished by the inhibitor, AMD3100. In clinical SRCC samples, CXCL12-secreting fibroblasts showed marked infiltration into the cancer area.

conclusionsE-cadherin deficient SRCCs might gain cell motility through upregulation of MMPs. CXCL12-positive cancer-associated fibroblasts could serve to maintain cancer-cell survival as a niche. MMPs and the CXCL12/CXCR4 axis represent promising candidates as novel therapeutic targets for E-cadherin-deficient SRCC.

Indexed as

Carcinoma, Signet Ring CellStomach NeoplasmsCadherinsGene Expression ProfilingGerm-Line MutationHumansCadherinsCDH1CXCR4Gastric cancerMatrix metalloproteinaseSignet ring carcinoma

Identifiers

PMID35661943
OpenAlexW4281663750

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.