DOCK4, a GTPase activator, is disrupted during tumorigenesis.

摘要: We used representational difference analysis to identify homozygous genomic deletions selected during tumor progression in the mouse NF2 and TP53 model. describe a deletion targeting DOCK4, member of CDM gene family encoding regulators small GTPases. DOCK4 specifically activates Rap GTPase, enhancing formation adherens junctions. mutations are present subset human cancer cell lines; recurrent missense mutant identified prostate ovarian cancers encodes protein that is defective Rap1 activation. The engulfment defect C. elegans mutants lacking ced-5 rescued by wild-type but not allele. Expression wild-type, mutant, osteosarcoma cells with endogenous suppresses growth soft agar invasion vivo. therefore regulates intercellular junctions disrupted tumorigenesis.