PDGFR-β-activated ACK1-AKT signaling promotes glioma tumorigenesis.

摘要: Aberrant PDGF-PDGFR signaling and its effects on downstream effectors have been implicated in glioma development. A crucial AKT regulator, ACK1 (TNK2) has shown to be a mediator of PDGF signaling; however, the exact underlying mechanisms gliomas remain elusive. Here, we report that cells, PDGFR-β activation enhanced interaction between AKT, resulting activation. treatment consistently promoted formation complexes containing ACK1. Mutational analysis suggested Y635 is phosphorylation site Y635F mutant abrogated sequential AKT. Moreover, PDK1 interacted with during stimulation, which required for binding PDGFR-β. Further mutational showed T325 was interaction. or T325A mutants abolished PDGFR-β-induced activation, subsequent nuclear translocation β-catenin expression cyclin D1. Glioma cell cycle progression, proliferation tumorigenesis were accordingly blocked by T325A. In glioblastoma multiforme samples from 51 patients, increased tyrosine correlated upregulated activity Taken together, our data demonstrate plays pivotal role PDGF-PDGFR-induced tumorigenesis. This knowledge contributes understanding progression may facilitate identification novel therapeutic targets future treatment.