作者: Zhong Wu , Charles Owens , Nidhi Chandra , Kay Popovic , Mark Conaway
DOI: 10.1593/NEO.101080
关键词: Bone metastasis 、 Ral GTP-Binding Proteins 、 Cancer research 、 Biology 、 Cell growth 、 Cell migration 、 RALA 、 Cancer 、 Molecular biology 、 Cancer cell 、 Metastasis
摘要: RalA expression in human prostate cancer is associated with cell migration and necessary for bone metastasis. However, the downstream effectors of that mediate these functions remain unclear. Here we examined after small interfering RNA-mediated depletion Ral binding protein 1 (RalBP1/RLIP), exocyst complex component 2 (Sec5), phospholipase D1 (PLD1) found RalBP1 inhibited to a similar extent. Stable lentivirus short hairpin PC3 cells metastasis intracardiac inoculation. Depletion diminished orthotopic tumor growth spontaneous from this site. Interestingly, wild-type or mutants deficient was effective at rescuing reduced metastatic capacity RalA-depleted cells, suggesting does not reduce solely by interaction RalBP1. To determine whether role relevant beyond cancer, studied requirement an experimental model bladder type high expression. UMUC3 resulted decreased lung colonization while having minimal effect on subcutaneous growth. Our studies are first suggest Furthermore, show manifestation phenotype entirely dependent RalA-RalBP1 interaction.