EphA2-YES1-ANXA2 pathway promotes gastric cancer progression and metastasis.
Animals
Annexin A2
/ genetics
Cell Line, Tumor
Cell Proliferation
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Neoplasm Metastasis
Phosphorylation
Proto-Oncogene Proteins c-yes
/ genetics
Receptor, EphA2
/ genetics
Signal Transduction
Stomach Neoplasms
/ genetics
Survival Rate
Xenograft Model Antitumor Assays
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
17
08
2020
accepted:
12
04
2021
revised:
31
03
2021
pubmed:
5
5
2021
medline:
15
1
2022
entrez:
4
5
2021
Statut:
ppublish
Résumé
Erythropoietin-producing hepatocellular receptor A2 (EphA2) is a key member of the receptor tyrosine kinase (RTK) family, while YES Proto-Oncogene 1 (YES1) is a non-receptor tyrosine kinase (nRTK) and annexin A2 (ANXA2) belongs to the calcium-dependent phospholipid-binding protein family annexins. Here, we show that EphA2, YES1, and ANXA2 form a signal axis, in which YES1 activated by EphA2 phosphorylates ANXA2 at Tyr24 site, leading to ANXA2 activation and increased ANXA2 nuclear distribution in gastric cancer (GC) cells. Overexpression (OE) of YES1 increases, while knockdown (KD) of YES1 or ANXA2 decreases GC cell invasion and migration in vitro and tumor growth in mouse models. Reexpression of wildtype (WT) rather than mutant ANXA2 (Tyr24F) in ANXA2 knockdown (ANXA2-KD) GC cells restores YES1-induced cell invasion and migration, while neither WT nor mutant ANXA2 (Tyr24F) can restore cell invasion and migration in YES1-KD GC cells. In addition, the activation of EphA2-YES1-ANXA2 pathway is correlated with poor prognosis. Thus, our results establish EphA2-YES1-ANXA2 axis as a novel pathway that drives GC invasion and metastasis, targeting this pathway would be an efficient way for the treatment of GC.
Identifiants
pubmed: 33941853
doi: 10.1038/s41388-021-01786-6
pii: 10.1038/s41388-021-01786-6
pmc: PMC8134040
doi:
Substances chimiques
ANXA2 protein, human
0
Annexin A2
0
EPHA2 protein, human
0
Receptor, EphA2
EC 2.7.10.1
Proto-Oncogene Proteins c-yes
EC 2.7.10.2
YES1 protein, human
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3610-3623Commentaires et corrections
Type : ErratumIn
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