Rad9 as part of the Rad9-Hus1-Rad1 complex is known to participate in cell cycle checkpoint activation and DNA repair. However, Rad9 can act as a sequence-specific
transcription factor, modulating expression of a number of genes. Importantly, Rad9 is up-regulated in
prostate cancer cell lines and clinical specimens. Its expression correlates positively with advanced stage
tumors and its down-regulation reduces
tumor burden in mice. We show here that transient down-regulation of Rad9 by RNA interference reduces DU145 and PC3
prostate cancer cell proliferation and survival in vitro. In addition, transient or stable down-regulation of Rad9 impairs migration and invasion of the cells. Moreover, stable reduction of Rad9 renders DU145 cell growth anchorage-dependent. It also decreases expression of
integrin β1
protein and sensitizes DU145 and LNCaP cells to anoikis and impairs Akt activation. On the other hand, stable expression of Mrad9, the mouse homolog, in DU145/
shRNA Rad9 cells restores migration, invasion, anchorage-independent growth,
integrin β1 expression, and anoikis resistance with a concomitant elevation of Akt activation. We thus demonstrate for the first time that Rad9 contributes to prostate
tumorigenesis by increasing not only
tumor proliferation and survival but also
tumor migration and invasion, anoikis resistance, and anchorage-independent growth.