PLAGL2 regulates actin cytoskeletal architecture and cell migration.

Pleomorphic adenoma gene like-2 (PLAGL2), a member of the PLAG gene family, is a C2H2 zinc finger transcriptional factor that is involved in cellular transformation and apoptosis. In this report, we show that PLAGL2 is associated with the organization of stress fibers and with small guanosine triphosphatase (GTPase) activity. Depletion of PLAGL2 in two different ovarian cancer cell lines, ES-2 and HEY, induced activation of RhoA, whereas activity of Rac1 was suppressed. Organization of actin stress fibers and focal adhesions was significantly promoted by PLAGL2 knockdown in a RhoA-dependent manner. Conversely, exogenous expression of PLAGL2 in MDA-MB-231 cells, a breast cancer cell line, resulted in the activation of Rac1 and the inactivation of RhoA. In addition, PLAGL2 expression induced lamellipodia formation and disruption of stress fiber formation. Finally, we show that CHN1 expression is essential for Rac1 inactivation in PLAGL2-depleted cells. Our results demonstrate a crucial role of PLAGL2 in actin dynamics and give further insight into the role of PLAGL2 in cellular transformation and apoptosis.