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http://ir.nhri.org.tw/handle/3990099045/10615
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| Title: | EZH2-mediated upregulation of ROS1 oncogene promotes oral cancer metastasis |
| Authors: | Shih, CH;Chang, YJ;Huang, WC;Jang, TH;Kung, HJ;Wang, WC;Yang, MH;Lin, MC;Huang, SF;Chou, SW;Chang, E;Chiu, H;Shieh, TY;Chen, YJ;Wang, LH;Chen, L |
| Contributors: | Institute of Molecular and Genomic Medicine |
| Abstract: | Current anti-epidermal growth factor receptor (EGFR) therapy for oral cancer does not provide satisfactory efficacy due to drug resistance or reduced EGFR level. As an alternative candidate target for therapy, here we identified an oncogene, ROS1, as an important driver for oral squamous cell carcinoma (OSCC) metastasis. Among tumors from 188 oral cancer patients, upregulated ROS1 expression strongly correlated with metastasis to lung and lymph nodes. Mechanistic studies uncover that the activated ROS1 results from highly expressed ROS1 gene instead of gene rearrangement, a phenomenon distinct from other cancers. Our data further reveal a novel mechanism that reduced histone methyltransferase EZH2 leads to a lower trimethylation of histone H3 lysine 27 suppressive modification, relaxes chromatin, and promotes the accessibility of the transcription factor STAT1 to the enhancer and the intron regions of ROS1 target genes, CXCL1 and GLI1, for upregulating their expressions. Down-regulation of ROS1 in highly invasive OSCC cells, nevertheless, reduces cell proliferation and inhibits metastasis to lung in the tail-vein injection and the oral cavity xenograft models. Our findings highlight ROS1 as a candidate biomarker and therapeutic target for OSCC. Finally, we demonstrate that co-targeting of ROS1 and EGFR could potentially offer an effective oral cancer therapy. |
| Date: | 2017-11 |
| Relation: | Oncogene. 2017 Nov;36(47):6542-6554. |
| Link to: | http://dx.doi.org/10.1038/onc.2017.262 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0950-9232&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000416049200004 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85035045780 |
| Appears in Collections: | [黃秀芬] 期刊論文
[龔行健] 期刊論文
[王陸海] 期刊論文
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| NMG2017080401.pdf | | 5192Kb | Adobe PDF | 411 | View/Open |
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