title: PLAGL2 regulates actin cytoskeletal architecture and cell migration.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology and Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sekiya
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Maeda
authors.affiliation: Department of Obstetrics and Gynecology and Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Asano
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hyodo
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Hitoki
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Obstetrics and Gynecology and Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Michinari
authors.initials: M
authors.lastname: Hamaguchi
authors.affiliation: Department of Obstetrics and Gynecology and Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
authors.affiliation: Department of Obstetrics and Gynecology and Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan tsenga@med.nagoya-u.ac.jp kajiyama@med.nagoya-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan tsenga@med.nagoya-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D020848:Chimerin 1 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D011554:Pseudopodia / Q000378:metabolism / Q000473:pathology; D016601:RNA-Binding Proteins / Q000502:physiology*; D022502:Stress Fibers / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020848:Chimerin 1; D004268:DNA-Binding Proteins; C114598:PLAGL2 protein, human; C107953:RAC1 protein, human; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C066737:RHOA protein, human; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein