title: Blockade of VEGF-A suppresses tumor growth via inhibition of autocrine signaling through FAK and AKT.
abstract: Blockade of VEGF signaling using RNA interferences, a neutralizing antibody, an antagonizing soluble VEGF receptor, and a receptor tyrosine kinase inhibitor induced anti-tumor effects in human astrocytoma U251-MG and fibrosarcoma HT-1080 in vitro in a dose-dependent manner. Furthermore, blockade of VEGF-A using the doxycycline-inducible VEGF-A RNA interference system showed a significant anti-tumor effect in a murine HT-1080-xenograft model. Anti-tumor effect through the blockade of VEGF signaling was mediated by FAK and AKT pathway in vitro and in vivo. These results collectively indicate that VEGF-A and its receptors can act as key inducer of tumor growth as well as angiogenesis.
authors.affiliation: Cell Signaling and Bio Imaging Laboratory, Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea.
authors.forename: Jungwhoi
authors.initials: J
authors.lastname: Lee
authors.forename: Taeyun
authors.initials: T
authors.lastname: Ku
authors.forename: Hana
authors.initials: H
authors.lastname: Yu
authors.forename: Kyuha
authors.initials: K
authors.lastname: Chong
authors.forename: Seung-Wook
authors.initials: SW
authors.lastname: Ryu
authors.forename: Kyungsun
authors.initials: K
authors.lastname: Choi
authors.forename: Chulhee
authors.initials: C
authors.lastname: Choi
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D045744:Cell Line, Tumor; D005354:Fibrosarcoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt