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.
Keywords:
Cervical cancer; VEGF-C; galectin-3; invasiveness.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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Blood Proteins
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Carcinoma / drug therapy
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Carcinoma / metabolism
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Carcinoma / pathology
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Cell Line, Tumor
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Female
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Galectin 3 / agonists
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Galectin 3 / antagonists & inhibitors
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Galectin 3 / genetics
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Galectin 3 / metabolism*
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Galectins
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Gene Silencing
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Humans
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Kinetics
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Neoplasm Invasiveness
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Neoplasm Proteins / agonists
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Phosphorylation
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Protein Processing, Post-Translational
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RNA, Small Interfering
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Recombinant Proteins / metabolism
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Signal Transduction* / drug effects
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Transcription Factor RelA / antagonists & inhibitors
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Transcription Factor RelA / genetics
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Transcription Factor RelA / metabolism*
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Up-Regulation*
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Uterine Cervical Neoplasms / drug therapy
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Uterine Cervical Neoplasms / metabolism*
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Uterine Cervical Neoplasms / pathology
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Vascular Endothelial Growth Factor C / genetics
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Vascular Endothelial Growth Factor C / metabolism*
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Vascular Endothelial Growth Factor Receptor-3 / agonists*
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Vascular Endothelial Growth Factor Receptor-3 / metabolism
Substances
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Antineoplastic Agents
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Blood Proteins
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Galectin 3
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Galectins
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LGALS3 protein, human
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Neoplasm Proteins
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RELA protein, human
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RNA, Small Interfering
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Recombinant Proteins
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Transcription Factor RelA
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VEGFC protein, human
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Vascular Endothelial Growth Factor C
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FLT4 protein, human
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Vascular Endothelial Growth Factor Receptor-3