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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/7242
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| Title: | LRIG1 modulates aggressiveness of head and neck cancers by regulating EGFR-MAPK-SPHK1 signaling and extracellular matrix remodeling |
| Authors: | Sheu, JJC;Lee, CC;Hua, CH;Li, CI;Lai, MT;Lee, SC;Cheng, J;Chen, CM;Chan, C;Chao, SCC;Chen, JY;Chang, JY;Lee, CH |
| Contributors: | National Institute of Cancer Research |
| Abstract: | EGFR overexpression and chromosome 3p deletion are two frequent events in head and neck cancers. We previously mapped the smallest region of recurrent copy-number loss at 3p12.2-p14.1. LRIG1, a negative regulator of EGFR, was found at 3p14, and its copy-number loss correlated with poor clinical outcome. Inducible expression of LRIG1 in head and neck cancer TW01 cells, a line with low LRIG1 levels, suppressed cell proliferation in vitro and tumor growth in vivo. Gene expression profiling, quantitative RT-PCR, chromatin immunoprecipitation, and western blot analysis demonstrated that LRIG1 modulated extracellular matrix (ECM) remodeling and EGFR-MAPK-SPHK1 transduction pathway by suppressing expression of EGFR ligands/activators, MMPs and SPHK1. In addition, LRIG1 induction triggered cell morphology changes and integrin inactivation, which coupled with reduced SNAI2 expression. By contrast, knockdown of endogenous LRIG1 in TW06 cells, a line with normal LRIG1 levels, significantly enhanced cell proliferation, migration and invasiveness. Such tumor-promoting effects could be abolished by specific MAPK or SPHK1 inhibitors. Our data suggest LRIG1 as a tumor suppressor for head and neck cancers; LRIG1 downregulation in cancer cells enhances EGFR-MAPK-SPHK1 signaling and ECM remodeling activity, leading to malignant phenotypes of head and neck cancers. |
| Date: | 2014-03 |
| Relation: | Oncogene. 2014 Mar;33(11):1375-1384. |
| Link to: | http://dx.doi.org/10.1038/onc.2013.98 |
| 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:000332943500005 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84896405445 |
| Appears in Collections: | [李家惠] 期刊論文
[張俊彥] 期刊論文
[陳振陽] 期刊論文
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| SCP84876695054.pdf | | 3176Kb | Adobe PDF | 886 | View/Open |
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