Exosome-mediated Delivery of the Intrinsic C-terminus Domain of PTEN Protects It From Proteasomal Degradation and Ablates Tumorigenesis

摘要: PTEN mutation is a frequent feature across plethora of human cancers, the hot-spot being its C-terminus (PTEN-CT) regulatory domain resulting in much diminished protein expression. In this study, presence mutations was confirmed through sequencing different tumor samples. The kinase CKII-mediated phosphorylation at these sites makes it loopy structure competing with E3 ligases for binding to lipid anchoring C2 domain. Accordingly, found that PTEN-CT expressing stable cell lines could inhibit tumorigenesis syngenic breast models. Therefore, we designed novel exosome-mediated delivery intrinsic domain, into cancer cells and observed reduced proliferation, migration, colony forming ability. exosome containing mice model result significant regression size sections showing increased apoptosis. Here, also report first time an active when bound by PTEN-CT, probably rendering anti-tumorigenic activities phosphatase activity. therapeutic interventions focus on ligase inhibition can be probable route treating cancers low