PUBLICATION
Blockage of LMP1-modulated store-operated Ca(2+) entry reduces metastatic potential in nasopharyngeal carcinoma cell
- Authors
- Wei, J., Zhang, J., Si, Y., Kanada, M., Zhang, Z., Terakawa, S., Watanabe, H.
- ID
- ZDB-PUB-150224-22
- Date
- 2015
- Source
- Cancer letters 360(2): 234-44 (Journal)
- Registered Authors
- Keywords
- Latent membrane protein 1, angiogenesis, metastasis, store-operated Ca(2+) entry
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Calcium/metabolism*
- Calcium Signaling
- Cell Line, Tumor
- Heterografts
- Human Umbilical Vein Endothelial Cells/pathology
- Humans
- Mice
- Mice, SCID
- Nasopharyngeal Neoplasms/blood
- Nasopharyngeal Neoplasms/metabolism*
- Nasopharyngeal Neoplasms/pathology*
- Nasopharyngeal Neoplasms/virology
- Neoplasm Metastasis
- Neoplastic Cells, Circulating/pathology*
- Viral Matrix Proteins/antagonists & inhibitors*
- Viral Matrix Proteins/metabolism
- Zebrafish
- PubMed
- 25697483 Full text @ Cancer Lett.
Citation
Wei, J., Zhang, J., Si, Y., Kanada, M., Zhang, Z., Terakawa, S., Watanabe, H. (2015) Blockage of LMP1-modulated store-operated Ca(2+) entry reduces metastatic potential in nasopharyngeal carcinoma cell. Cancer letters. 360(2):234-44.
Abstract
Epstein-Barr virus (EBV)-encoded latent membrane proteins (LMPs) expedite progression of EBV-relevant cancers. Of the full set of LMPs, latent membrane protein 1 (LMP1) was identified to uniquely augment store-operated Ca(2+) entry (SOCE). Previously, we reported that the suppression of SOCE exhibited inhibitory effects on cell migration and the extravasation from vasculature in EBV-negative nasopharyngeal carcinoma (NPC) cells. In this follow-up study, we aimed to expand our understanding of the modulation of SOCE by LMP1 and test the possibility that blockage of LMP1-modulated SOCE affects the LMP1-promoted metastatic potential. Here we showed that suppressions of the LMP1-boosted SOCE blunted the LMP1-promoted cell migration, VEGF-mediated angiogenesis and permeabilization in vitro. Blockage of SOCE inhibited vasculature-invasion of circulating cells and distant metastatic colonization in vivo. Notably, utilizing VEGFR2-EGFP-tag zebrafish we revealed that the LMP1-expressing cells arrested in a small-caliber vessel mobilized surrounding endothelial cells to facilitate vasculature-invasion. Thus, the LMP1-boosted SOCE promotes metastatic potential of NPC cells by solidifying their collaborations with the nearby non-cancer cells through the manipulation of oncogenic Ca(2+) signaling. Our study highlights the advantage of using both conventional mammal and transgenic zebrafish for developing a novel therapeutic strategy targeting the multiple steps of invasion-metastasis cascade.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping