[en] RhoGDI2 is a RhoGTPase regulator that has roles in cytoskeleton organization and cell survival, amongst others. It is differentially expressed in many cell types and tissues, including several human cancers where its expression has been correlated to either good or bad prognosis. To identify the underlying mechanisms, we knocked down its expression in U2OS and MG-63 human osteosarcoma cell lines. We observed that repression of RhoGDI2 expression in these cells, but not that of the closely related RhoGDI1, significantly reduces their proliferation rate. Searching for mechanisms explaining such effect, we found that RhoGDI2 silencing promotes mitotic errors and centrosomal abnormalities. RhoGDI2 suppression aggravates supernumerary centrosomes and spindle defects while inhibiting ciliogenesis. As Rho GTPases are also implicated in ciliary defects, we checked if suppression of key Rho GTPases affects ciliogenesis in RhoGDI2-silenced cells. We observed that the silencing of Cdc42 and RhoA, but not Rac1, partially rescue the ciliary defects observed upon RhoGDI2 silencing. Considering the striking similarities between primary cilia and immune synapses, we next verified if RhoGDI2 also affects centrosomal functions in NK-92 (natural killer) cells. When a natural killer cell recognizes an infected cell, the centrosome forms the immunological synapse (IS) with the target cell to initiate the killing process. We observed that knocking down RhoGDI2 in NK-92 significantly reduces their tumor-killing abilities, thereby hinting at the cells’ potential loss of IS. These data suggest a novel role for RhoGDI2 in centrosomal functions in human cancer and immune cells, also possibly explaining its dual role in cancer.
