EB virus promotes metastatic potential by boosting STIM1-dependent Ca2+ signaling in nasopharyngeal carcinoma cells. (28th May 2020)

• Record Type: Journal Article
• Authors: Wei, Jiazhang; Ye, Jiaxiang; Luo, Yue; Weng, Jingjin; He, Qian; Liu, Fei; Li, Min; Lin, Yan; Li, Yongqiang; Zhang, Zhe; Qu, Shenhong; Zhang, Jinyan
• Is Part Of: Cancer letters. Volume 478(2020)
• Page Start: 122
• Page End: 132
• Publication Date: 2020-05-28
• Subjects: Epstein–barr virus -- STIM1 -- Epithelial-mesenchymal transition -- Migration -- Metastasis; EBV Epstein–Barr virus -- NPC nasopharyngeal carcinoma -- LMP latent membrane protein -- SOCE store-operated Ca2+ entry -- EGF epidermal growth factor -- EMT epithelial-mesenchymal transition -- EGFP enhanced green fluorescent protein -- FRET fluorescence resonance energy transfer -- hpf hours post-fertilization -- NNE normal nasopharyngeal epithelium; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2020.03.005
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Nasopharyngeal carcinoma (NPC) is a unique head and neck malignancy with highly metastatic cell-biological characteristics, for which latent EBV-infection is responsible. Our earlier studies showed that EGF-stimulated Ca 2+ signaling via store-operated Ca 2+ entry (SOCE) was amplified in NPC cells expressing EBV-encoded LMP1, thus contributing to EBV-enhanced metastatic capacities. However, the pathway through which EBV modulates cytosolic Ca 2+ signaling still remains unclear. Here, we demonstrated that EBV-infection amplified EGF-stimulated Ca 2+ responses through the promotion of intracellular aggregation of STIM1, which serves as a Ca 2+ sensor to activate SOCE. Blockage of EBV-remodeled Ca 2+ signaling by STIM1-silencing inhibited cell migration by interrupting epithelial-mesenchymal transition (EMT) in vitro, and suppressed tumor dissemination in zebrafish and lymph node metastasis in mice. In addition, STIM1 expression was upregulated in primary NPC tissues compared with normal nasopharyngeal epithelium and stronger among the patients with advanced lymph node metastatic disease (N2-3 stage). Our findings thus indicate that EBV promotes metastatic potential by enhancing STIM1-dependent Ca 2+ signaling that manipulates EMT in NPC cells. EBV-modulated Ca 2+ signaling could serve as a candidate anti-metastatic target for NPC treatment. Highlights: The FRET-based Ca 2+ probe was utilized to characterize EBV-related malignant profiles. A zebrafish model was employed to study NPC dissemination at a single-cell level. STIM1-dependent Ca 2+ signaling mediates EBV-promoted invasion and metastasis in NPC.