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EphA2 regulates vascular permeability and prostate cancer metastasis via modulation of cell junction protein phosphorylation.


ABSTRACT: Prostate cancer morbidity and mortality demonstrate a need for more effective targeted therapies. One potential target is EphA2, although paradoxically, pro- and anti-oncogenic effects have been shown to be mediated by EphA2. We demonstrate that unique activating and blocking EphA2-targeting monoclonal antibodies display opposing tumor-suppressive and oncogenic properties in vivo. To further explore this complexity, we performed detailed phosphoproteomic analysis following ligand-induced EphA2 activation. Our analysis identified altered phosphorylation of 73 downstream proteins related to the PI3K/AKT/mTOR and ERK/MAPK pathways, with the majority implicated in cell junction and cytoskeletal organization, cell motility, and tumor metastasis. We demonstrate that the adapter protein SHB is an

SUBMITTER: Offenhauser C 

PROVIDER: S-EPMC11753358 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature