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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/3756
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| Title: | Endoplasmic reticulum stress triggers XBP-1-mediated up-regulation of an EBV oncoprotein in nasopharyngeal carcinoma |
| Authors: | Hsiao, JR;Chang, KC;Chen, CW;Wu, SY;Su, IJ;Hsu, MC;Jin, YT;Tsai, ST;Takada, K;Chang, Y |
| Contributors: | Division of Infectious Diseases |
| Abstract: | Endoplasmic reticulum (ER) stress-activated unfolded protein response (UPR) plays multiple roles in cancer development, but its specific roles for virus-associated cancers have not been fully understood. It is still unknown whether ER stress/ UPR occurs in and contributes to nasopharyngeal carcinoma (NPC), an epithelial malignancy closely associated with EBV. Here, we report that UPR proteins are frequently detected in NPC biopsies. In addition, we reveal that, in EBV-infected NPC cells, ER stress inducers up-regulate a potent EBV oncoprotein latent membrane protein 1 (LMP1), and the ER stress-induced LMP1 enhances production of interleukin-8. ER stress triggers LMP1 expression at a transcriptional level, activating a distal LMP1 promoter TR-L1. TR-L1 contains an ER stress-responsive element, which is targeted by an UPR protein XBP-1. Ectopic expression of XBP-1 induces LMP1 expression, and knockdown of XBP-1 blocks ER stress-triggered upregulation of LMP1 in NPC cells. Furthermore, XBP-1 significantly correlates with LMP1 expression in NPC tumor biopsies. Therefore, this study not only provides a novel clue linking ER stress/UPR to EBV-associated NPC but also suggests that ER stress/UPR can promote virus-associated cancer in a unique way by driving expression of a viral oncogene. |
| Date: | 2009-05-15 |
| Relation: | Cancer Research. 2009 May 15;69(10):4461-4467. |
| Link to: | http://dx.doi.org/10.1158/0008-5472.can-09-0277 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000266214400046 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=66249135326 |
| Appears in Collections: | [張堯] 期刊論文
[蘇益仁(2002-2015)] 期刊論文
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| SCP66249135326.pdf | | 461Kb | Adobe PDF | 826 | View/Open |
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