Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 503, Issue 3, Pages 2160-2166Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.08.006
Keywords
Epstein-Barr virus; Rta; Nasopharyngeal carcinoma; Matrix metalloproteinase 9; Cell invasion
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Funding
- Ministry of Science and Technology, Taiwan [NSC-102-2628-B-400-001-MY3, MOST-105-2320-B-400-010-MY3, MOST-107-2320-B-471-001]
- National Health Research Institutes, Taiwan [IV-103-PP-19, IV-104-PP-19, IV-105-PP-17, IV-106-PP-15, IV-107-PP-15]
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Clinical studies suggest a positive association between malignant progression of nasopharyngeal carcinoma (NPC) and Rta, a transcription factor of Epstein-Barr virus (EBV). However, Rta induces cellular senescence in vitro. To provide an underlying mechanism integrating these clues, we adapted a concept of senescence-associated secretory phenotype (SASP), based on which senescent cells facilitate tumor progression through paracrine. First, Rta-expressing NPC cells themselves show reduced invasiveness but promote invasion of Rta-negative tumor cells through secreted factors. Secretion of matrix metalloproteinase 9 (MMP9), an SASP protein, is increased by Rta, which requires the C-terminus of Rta and Rta-induced activation of E2F. Furthermore, the Rta-induced, paracrine-mediated pro-invasive effect is blocked upon knockdown of MMP9 expression or treatment with an MMP9 inhibitor. This study not only indicates that Rta can contribute to NPC progression through paracrine but also supports that MMP9 is a potential therapeutic target to prevent NPC metastasis. (C) 2018 Elsevier Inc. All rights reserved.
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