The Hippo Pathway Effector YAP/TEAD Regulates EPHA3 Expression and Functions

Cell-cell interaction is critical for tissue development and repair, immunological responses, cancer cell metastasis. The tyrosine kinase EPHA3 (erythropoietin‑producing hepatocellular carcinoma surface type-A receptor 3) regulates cell-cell interaction, differentiation, survival. Previously, our published study indicated that the STK4-encoded MST1 signaling, a core component of Hippo pathway, suppressed expression in prostate models. However, mechanism unknown. Here, we have demonstrated YAP1 TEAD1 proteins, nuclear effectors mediate expression. First, showed AR-positive lines express highest levels its ligand ephrin-A5 transcripts compared with other EPH family members. Second, induction MST1/STK4 attenuated protein transcripts, consistent initial observation. Next, knockdown by siRNA mRNA Similarly, silencing TEAD1-4 mediators YAP1-dependent gene transcription, revealed crucial inducer Moreover, bioinformatics tools allowed identification three putative TEAD binding sites (p<0.001) promoter region gene. Furthermore, CRISPER/Cas9-aided knockout significantly (p<0.01), decreased growth monolayer sphere formation 3D cultures caused androgen-independent cells to become sensitive enzalutamide, potent direct inhibitor AR activity. These observations suggest YAP/TEAD1 transcriptionally cellular biology.