EphA2-YES1-ANXA2 pathway promotes gastric cancer progression and metastasis.

ABSTRACT: 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 restore

SUBMITTER: Mao L 

PROVIDER: S-EPMC8134040 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature