國家衛生研究院 NHRI:Item 3990099045/10036
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10036


    Title: Molecular mechanisms of DUSP22 ablation in enhancing EGFR-mediated lung tumor development: Potential involvement of immunosuppression
    Authors: Lin, HP;Ho, HM;Chang, CW;Tan, TH;Lin, WJ
    Contributors: Immunology Research Center
    Abstract: DUSP22, a member of the dual-specificity phosphatases (DUSPs) family, is a key phosphatase controlling the activity of protein kinases and transcription factors through the dephosphorylation (serine/threonine or tyrosine) process, such as MAPKs, FAK, Lck, and STAT3. Many members of DUSP22-targeted proteins are important for tumorigenesis, and DUSP22 downregulation has been reported in some cancers. Importantly, DUSP22 -/- mice manifest multi-organ inflammation, supporting a role for DUSP22 in maintaining immune homeostasis. However, little is known about the in vivo role of DUSP22 during tumor development. Here, utilizing a murine lung tumor model driven by the combination of mutated EGFR amplification (exon 19 deletion) and the loss of DUSP22, we found genetic ablation of DUSP22 promoted aggressive EGFR-mediated lung tumor development at early age, and identified MDSCs and exhausted T cells as the two main tumor-infiltrating immune cell types. Our cytokine array profiling found a significant increase of IL-1 and CXCL1 in EGFR/DUSP22 KO lung tumors, suggesting these two cytokines may potentially serve as EGFR/DUSP22 KO tumor-derived factors to attract immuosuppressive cells and promote tumor development. Consistently, GEO data analysis shows that lung adenocarcinoma patients with low DUSP22 expression have poor survival. Collectively, our current data indicate that DUSP22 underexpression may facilitate the recruitment of MDSCs and dysfunctional T cells and establish an immunosuppressive tumor microenvironment for tumor development. Currently, we are using pharmacological and immune approach to elucidate molecular mechanisms of DUSP22 ablation for enhancing lung tumor development.
    Date: 2016-08
    Relation: European Journal of Immunology. 2016 Aug;46(Suppl. 1):240.
    Link to: http://dx.doi.org/10.1002/eji.201670200
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0014-2980&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000383610400485
    Appears in Collections:[Wen-Jye Lin] Conference Papers/Meeting Abstract
    [Tse-Hua Tan] Conference Papers/Meeting Abstract

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