title: The signaling network of transforming growth factor beta1, protein kinase Cdelta, and integrin underlies the spreading and invasiveness of gastric carcinoma cells.
abstract: Integrin-mediated cell adhesion and spreading enables cells to respond to extracellular stimuli for cellular functions. Using a gastric carcinoma cell line that is usually round in adhesion, we explored the mechanisms underlying the cell spreading process, separate from adhesion, and the biological consequences of the process. The cells exhibited spreading behavior through the collaboration of integrin-extracellular matrix interaction with a Smad-mediated transforming growth factor beta1 (TGFbeta1) pathway that is mediated by protein kinase Cdelta (PKCdelta). TGFbeta1 treatment of the cells replated on extracellular matrix caused the expression and phosphorylation of PKCdelta, which is required for expression and activation of integrins. Increased expression of integrins alpha2 and alpha3 correlated with the spreading, functioning in activation of focal adhesion molecules. Smad3, but not Smad2, overexpression enhanced the TGFbeta1 effects. Furthermore, TGFbeta1 treatment and PKCdelta activity were required for increased motility on fibronectin and invasion through matrigel, indicating their correlation with the spreading behavior. Altogether, this study clearly evidenced that the signaling network, involving the Smad-dependent TGFbeta pathway, PKCdelta expression and phosphorylation, and integrin expression and activation, regulates cell spreading, motility, and invasion of the SNU16mAd gastric carcinoma cell variant.
authors.affiliation: Cancer Research Institute, College of Medicine, Seoul National University, Republic of Korea.
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Lee
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Kim
authors.forename: Yong-Bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Sung-Yul
authors.initials: SY
authors.lastname: Lee
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Ko
authors.forename: Hyun-Soon
authors.initials: HS
authors.lastname: Jong
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Lee
mesh_terms: D015153:Blotting, Western; D002448:Cell Adhesion; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D039421:Integrin alpha2 / Q000378:metabolism; D039422:Integrin alpha3 / Q000378:metabolism; D007797:Laminin / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D011509:Proteoglycans / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014945:Wound Healing
chemical_list: D004338:Drug Combinations; D005353:Fibronectins; D039421:Integrin alpha2; D039422:Integrin alpha3; D007797:Laminin; D011509:Proteoglycans; D034741:RNA, Small Interfering; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C059485:matrigel; D049452:Green Fluorescent Proteins; D003094:Collagen; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta