Evidence map›Paper›PMID 37016377›Full record

ArticleJournal of experimental & clinical cancer research : CR2023

FYN/TOPK/HSPB1 axis facilitates the proliferation and metastasis of gastric cancer.

SanFei Peng, YuHan Yin, YiZheng Zhang, Feng Zhu, Ge Yang, Yang Fu

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 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

6 authors at 2 institutions in 1 country.

SanFei PengDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou, University, Zhengzhou, 450052, China.
YuHan YinDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou, University, Zhengzhou, 450052, China.
YiZheng ZhangDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou, University, Zhengzhou, 450052, China.
Feng ZhuCancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, 541000, Guangxi, China.
Ge YangDepartment of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. younglioness@163.com.
Yang FuDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou, University, Zhengzhou, 450052, China. fuyang@zzu.edu.cn.ORCID http://orcid.org/0000-0002-8221-3354
First Affiliated Hospital of Zhengzhou University · CNGuilin Medical University · CN

Funding

National Natural Science Foundation of China 81871995Natural Science Foundation of Henan Province 212300410075
6 · The paper itself

Abstract

backgroundFYN is a nonreceptor tyrosine kinase that regulates diverse pathological processes. The pro-cancer role of FYN in multiple malignancies has been elucidated. However, the mechanisms that FYN promotes gastric cancer (GC) progression remain largely unknown.

methodsIn vitro and in vivo assays were used to investigate the function of FYN. FYN, TOPK, p-TOPK expression in GC specimens were detected by immunohistochemistry. Phosphoproteomics assays identify TOPK downstream substrate molecules. The molecular mechanism was determined using COIP assays, pull-down assays, immunofluorescence co-localization assays, western blotting,

resultsFYN was found to be significantly upregulated in GC tissues as well as in GC cells. Knockdown of FYN expression markedly attenuated the malignant phenotype of GC cells in vitro and in vivo. Mechanistically, we identified TOPK/PBK as a novel downstream substrate of FYN, FYN directly phosphorylates TOPK at Y272. One phosphospecific antibodies against Y272 was developed to validate the phosphorylation of TOPK by FYN. Moreover, the TOPK-272F mutation impaired the interaction between TOPK and FYN, leading to disappeared TOPK phosphorylation. Consistently, human GC tissues displayed increased p-TOPK(Y272), which correlated with poor survival. Phosphoproteomics results showed a significant downregulation of both HSPB1 and p-HSPB1(ser15) in TOPK-knockdown cells, which was confirmed by TOPK-konckout mice.

conclusionsFYN directly binds to TOPK in GC cells and phosphorylates TOPK at the Y272, which leads to proliferation and metastasis of GC. FYN-TOPK axis facilitates GC progression by phosphorylating HSPB1. Collectively, our study elucidates the pivotal role of the FYN-TOPK-HSPB1 cascade in GC.

Indexed as

Mitogen-Activated Protein Kinase KinasesStomach NeoplasmsAnimalsCell Line, TumorCell ProliferationHeat-Shock ProteinsHumansMiceMolecular ChaperonesPhosphorylationHeat-Shock ProteinsHSPB1 protein, humanMitogen-Activated Protein Kinase KinasesMolecular ChaperonesFYNGastric Cancer ProgressionHSPB1PhosphorylationTOPK

Identifiers

PMID37016377
PMCPMC10071617
OpenAlexW4362554990

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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.