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Yes-associated protein (YAP) is a transcriptional coactivator that promotes cell proliferation, stem cell maintenance and tissue homeostasis. The YAP activity is primarily regulated through an inhibitory phosphorylation by the serine/threonine kinases of Hippo pathway. Here, we show that receptor tyrosine kinase (RTK) erythropoietin-producing hepatocellular receptor A2 (EphA2) interacts with and phosphorylates YAP protein, leading to stabilization, nuclear translocation and activation of YAP in gastric cancer (GC) cells. EphA2 induces chemotherapy-resistance by increasing YAP stability and nuclear YAP protein. Knockdown of YAP blocks EphA2-induced tumor growth in GC xenograft mouse models. Importantly, the coactivation of EphA2 and YAP is manifested in clinical human GC, and is related to GC recurrence. Thus, our results establish a novel EphA2-to-YAP pathway that drives GC growth, progression and therapy-resistance, targeting this pathway would be an efficient way for the treatment of GC, particularly chemotherapy-resistant GC.
Pubmed ID: 31376289
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This recombinant monoclonal targets YAP
View all literature mentionsThis monoclonal targets Phospho-EphA2 (Ser897) (D9A1) Rabbit mAb
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets YAP1, phospho (Tyr357)
View all literature mentionsThis monoclonal targets EphA2 (D4A2) XP Rabbit mAb
View all literature mentionsCell line KATO III is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-N87 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line AGS is a Cancer cell line with a species of origin Homo sapiens (Human)
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