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DOI | 10.1038/ncomms14163 |
LNK suppresses interferon signaling in melanoma | |
Ding, Ling-Wen1; Sun, Qiao-Yang1; Edwards, Jarem J.2,3; Fernandez, Lucia Torres1; Ran, Xue-Bin1; Zhou, Si-Qin1; Scolyer, Richard A.2,3,4; Wilmott, James S.2,3; Thompson, John F.2,3,4; Ngan Doan5; Said, Jonathan W.5; Venkatachalam, Nachiyappan1; Xiao, Jin-Fen1; Loh, Xin-Yi1; Pein, Maren1; Xu, Liang1; Mullins, David W.6,7; Yang, Henry1; Lin, De-Chen8; Koeffler, H. Phillip1,8 | |
2019-05-20 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | Singapore; Australia; USA |
英文摘要 | LNK (SH2B3) is a key negative regulator of JAK-STAT signaling which has been extensively studied in malignant hematopoietic diseases. We found that LNK is significantly elevated in cutaneous melanoma; this elevation is correlated with hyperactive signaling of the RAS-RAF-MEK pathway. Elevated LNK enhances cell growth and survival in adverse conditions. Forced expression of LNK inhibits signaling by interferon-STAT1 and suppresses interferon (IFN) induced cell cycle arrest and cell apoptosis. In contrast, silencing LNK expression by either shRNA or CRISPR-Cas9 potentiates the killing effect of IFN. The IFN-LNK signaling is tightly regulated by a negative feedback mechanism; melanoma cells exposed to IFN upregulate expression of LNK to prevent overactivation of this signaling pathway. Our study reveals an unappreciated function of LNK in melanoma and highlights the critical role of the IFN-STAT1-LNK signaling axis in this potentially devastating disease. LNK may be further explored as a potential therapeutic target for melanoma immunotherapy. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000468274600010 |
WOS关键词 | IMMUNE-CHECKPOINT BLOCKADE ; MOUSE HEMATOPOIETIC STEM ; PD-1 BLOCKADE ; ACQUIRED-RESISTANCE ; CANCER ; JAK2 ; THERAPY ; BRAF ; MUTATIONS ; ANTI-PD-1 |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203172 |
专题 | 资源环境科学 |
作者单位 | 1.Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117599, Singapore; 2.Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2065, Australia; 3.Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia; 4.Royal Prince Alfred Hosp, Sydney, NSW 2050, Australia; 5.Santa Monica Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90095 USA; 6.Geisel Sch Med Dartmouth, Dept Med Educ, Dartmouth, MA 03755 USA; 7.Geisel Sch Med Dartmouth, Dept Microbiol Immunol, Dartmouth, MA 03755 USA; 8.Univ Calif Los Angeles, Cedars Sinai Med Ctr, Div Hematol Oncol, Sch Med, Los Angeles, CA 90048 USA |
推荐引用方式 GB/T 7714 | Ding, Ling-Wen,Sun, Qiao-Yang,Edwards, Jarem J.,et al. LNK suppresses interferon signaling in melanoma[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Ding, Ling-Wen.,Sun, Qiao-Yang.,Edwards, Jarem J..,Fernandez, Lucia Torres.,Ran, Xue-Bin.,...&Koeffler, H. Phillip.(2019).LNK suppresses interferon signaling in melanoma.NATURE COMMUNICATIONS,10. |
MLA | Ding, Ling-Wen,et al."LNK suppresses interferon signaling in melanoma".NATURE COMMUNICATIONS 10(2019). |
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