title: Downregulation of G3BPs inhibits the growth, migration and invasion of human lung carcinoma H1299 cells by suppressing the Src/FAK-associated signaling pathway.
abstract: G3BP is a RasGAP binding protein that is overexpressed in many human cancers. We previously reported that downregulation of G3BP suppressed cell growth and induced apoptosis in HCT116 cells. Here we report that both transient and stable knockdown of G3BP suppressed the growth, migration and invasion capability of human lung carcinoma H1299 cells. Moreover, downregulation of G3BP significantly inhibited the phosphorylation of Src, FAK and ERK, and the levels of NF-κB were also markedly decreased in H1299 cells. Knockdown of G3BP also decreased the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and plasminogen activator (uPA), and in vivo data demonstrated that downregulation of G3BP markedly inhibited the growth of H1299 tumor xenografts. Together, these data revealed that knockdown of G3BP inhibited the migration and invasion of human lung carcinoma cells through the inhibition of Src, FAK, ERK and NF-κB and decreased levels of MMP-2, MMP-9 and uPA.
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: S-h
authors.initials: SH
authors.lastname: Zhang
authors.forename: H-w
authors.initials: HW
authors.lastname: He
authors.forename: C-x
authors.initials: CX
authors.lastname: Zhang
authors.forename: D-k
authors.initials: DK
authors.lastname: Yu
authors.forename: R-g
authors.initials: RG
authors.lastname: Shao
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004265:DNA Helicases; D015536:Down-Regulation; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D016328:NF-kappa B; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D034741:RNA, Small Interfering; D051417:Focal Adhesion Kinase 1; D019061:src-Family Kinases; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases