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: Junxiu Liu, Yang Cheng, Mian He, Shuzhong Yao
• Journal: Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology (Gynecol Endocrinol) Vol. 30 Issue 6 Pg. 461-5 (Jun 2014) ISSN: 1473-0766 [Electronic] England
• PMID: 24650367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Blood Proteins
• Galectin 3
• Galectins
• LGALS3 protein, human
• Neoplasm Proteins
• RELA protein, human
• RNA, Small Interfering
• Recombinant Proteins
• Transcription Factor RelA
• VEGFC protein, human
• Vascular Endothelial Growth Factor C
• FLT4 protein, human
• Vascular Endothelial Growth Factor Receptor-3

Topics

• Antineoplastic Agents (pharmacology)
• Blood Proteins
• Carcinoma (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Female
• Galectin 3 (agonists, antagonists & inhibitors, genetics, metabolism)
• Galectins
• Gene Silencing
• Humans
• Kinetics
• Neoplasm Invasiveness
• Neoplasm Proteins (agonists, antagonists & inhibitors, genetics, metabolism)
• Phosphorylation
• Protein Processing, Post-Translational
• RNA, Small Interfering
• Recombinant Proteins (metabolism)
• Signal Transduction (drug effects)
• Transcription Factor RelA (antagonists & inhibitors, genetics, metabolism)
• Up-Regulation
• Uterine Cervical Neoplasms (drug therapy, metabolism, pathology)
• Vascular Endothelial Growth Factor C (genetics, metabolism)
• Vascular Endothelial Growth Factor Receptor-3 (agonists, metabolism)