title: Hepatoma-derived growth factor stimulates podosome rosettes formation in NIH/3T3 cells through the activation of phosphatidylinositol 3-kinase/Akt pathway.
abstract: Hepatoma-derived growth factor (HDGF) stimulates the migration, invasion and metastasis in several types of cancer cells. However, the mechanism underlying HDGF-stimulated migration remains unclear. In this study, we investigated the influence of HDGF on cytoskeleton remodeling and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in non-transformed NIH/3T3 cells. Exogenous HDGF promoted the migration and the formation of dorsal ruffles and podosome rosettes. Besides, HDGF supply increased the PI3K expression and Akt phosphorylation in dose- and time-dependent manners. Application of LY294002, a PI3K inhibitor, attenuated the HDGF-induced migration, dorsal ruffles and podosome rosettes formation. Consistently, the HDGF-overexpressing NIH/3T3 transfectants exhibited significantly increased motility and elevated PI3K/Akt activities, which were repressed by LY294002 or adenovirus-mediated overexpression of endogenous PI3K antagonist, PTEN. In summary, HDGF elicits the activation of PI3K/Akt signaling cascade, thereby promoting cytoskeleton remodeling to stimulate cellular migration.
authors: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC.
authors: Mei-Lang
authors: ML
authors: Kung
authors: Han-En
authors: HE
authors: Tsai
authors: Tsung-Hui
authors: TH
authors: Hu
authors: Hsiao-Mei
authors: HM
authors: Kuo
authors: Li-Fen
authors: LF
authors: Liu
authors: San-Cher
authors: SC
authors: Chen
authors: Pey-Ru
authors: PR
authors: Lin
authors: Yi-Ling
authors: YL
authors: Ma
authors: E-Ming
authors: EM
authors: Wang
authors: Guei-Sheung
authors: GS
authors: Liu
authors: Jong-Kang
authors: JK
authors: Liu
authors: Ming-Hong
authors: MH
authors: Tai
mesh_terms: D000818:Animals; D002465:Cell Movement; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D058539:Phosphatidylinositol 3-Kinase / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D012397:Rosette Formation; D014162:Transfection
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt