title: Vascular endothelial growth factor C enhances cervical cancer cell invasiveness via upregulation of galectin-3 protein.
abstract: Vascular endothelial growth factor C (VEGF-C) promotes cervical cancer metastasis, while the detailed mechanism remains obscure. Recent evidence shows that galectin-3 (Gal-3), a glycan binding protein, interacts with the VEGF receptors and reinforces their signal transduction. In this study, we investigated the role of Gal-3 in VEGF-C-induced cervical cancer cell invasion. On cervical carcinoma cell line SiHa cells, silencing of Gal-3 expression with specific siRNA largely impaired VEGF-C-enhanced cell invasion. Treatment with VEGF-C for 12-48 h enhanced Gal-3 protein expression, which was inhibited by the addition of NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). Moreover, the silencing of NF-κB subunit p65 expression with specific siRNA attenuated VEGF-C-enhanced Gal-3 expression, suggesting that NF-κB is the key intermediate. Under VEGF-C stimulation, an enhanced interaction between VEGF receptor-3 (VEGF-R3) and Gal-3 was found, which may possibly lead to VEGF-R3 activation since exogenous Gal-3 induced VEGF-R3 phosphorylation in a dose- and time-dependent manner. In conclusion, our findings implied that VEGF-C enhanced cervical cancer invasiveness via upregulation of Gal-3 protein through NF-κB pathway, which may shed light on potential therapeutic strategies for cervical cancer therapy.
authors.affiliation: Department of Gynecology and Obstetrics, The First Affiliated Hospital of Sun Yat-Sen University , Guangdong, Guangzhou , China and.
authors.forename: Junxiu
authors.initials: J
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Cheng
authors.forename: Mian
authors.initials: M
authors.lastname: He
authors.forename: Shuzhong
authors.initials: S
authors.lastname: Yao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001798:Blood Proteins; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D037502:Galectin 3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D037161:Galectins; D020868:Gene Silencing; D006801:Humans; D007700:Kinetics; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000819:agonists* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; D009363:Neoplasm Proteins; C498143:RELA protein, human; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D051996:Transcription Factor RelA; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; C581309:FLT4 protein, human; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Cervical cancer; VEGF-C; galectin-3; invasiveness