RanBP9/TSSC3 complex cooperates to suppress anoikis resistance and metastasis via inhibiting Src-mediated Akt signaling in osteosarcoma.

ABSTRACT: Suppression of anoikis is a prerequisite for tumor cell metastasis, which is correlated with chemoresistance and poor prognosis. We characterized a novel interaction between RanBP9 SPRY domain and TSSC3 PH domain by which RanBP9/TSSC3 complex exerts transcription and post-translation regulation in osteosarcoma. RanBP9/TSSC3 complex was inversely correlated with a highly anoikis-resistant phenotype in osteosarcoma cells and metastasis in human osteosarcoma. RanBP9 cooperated with TSSC3 to inhibit anchorage-independent growth and to promote anoikis in vitro and suppress lung metastasis in vivo. Moreover, RanBP9 SPRY domain was required for RanBP9/TSSC3 complex-mediated anoikis resistance. Mechanistically, RanBP9 formed a ternary complex with TSSC3 and Src to scaffold this interaction, which

SUBMITTER: Dai H 

PROVIDER: S-EPMC5261021 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature