The Role of Eph a Receptor 3 (Epha3) Tyrosine Kinase Signaling in Prostate Cancer
Mathkour, Marwah M., Clark Atlanta University
2022-05
2020-2029
The Hippo pathway regulates diverse biological processes, including cell growth, organ size and carcinogenesis by modulating cell contact. Cell contact is critical for tissue development and repair, immunological responses, and cancer cell metastasis. A published study suggested that the STK4-encoded MST1, a core kinase component of the Hippo pathway, could attenuate EPHA3 expression in the prostate cancer cell models. However, the mechanism of how it occurs is unknown. The present study demonstrated that the transcriptional regulatory proteins YAP1 and TEAD1, critical nuclear effectors of the Hippo pathway, promote EPHA3 expression. Gene expression analysis showed that AR-positive cell lines expressed the highest levels of EPHA3 and its ligand ephrin-A5 compared with other Ephrin receptor family members. In addition, the induction of MST1 attenuated the EPHA3 protein and transcripts, consistent with the initial observation. Moreover, the silencing of YAP1 by siRNA suppressed EPHA3 protein and mRNA expression. Similarly, the silencing of the TEAD1-4 proteins, critical mediators of YAP1-dependent gene transcription, reduced EPHA3 expression. Furthermore, the distal EPHA3 promoter harbors three putative TEAD responsive elements where YAP1 and TEAD1 bind and drive EPHA3 expression. These findings demonstrate that EPHA3 is a novel target of the Hippo pathway and that YAP in concert with the TEAD1 transcriptionally regulates EPHA3 expression and its cellular biology.
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Atlanta University and Clark Atlanta University Theses and Dissertations
dissertation
Doctor of Philosophy (PhD)
Clark Atlanta University
Department of Biological Sciences
Cinar, Bekir
Georgia--Atlanta
http://hdl.handle.net/20.500.12322/cau.td:2022_mathkour_marwah_m
http://rightsstatements.org/vocab/InC-EDU/1.0/
