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| Status |
Public on Mar 31, 2019 |
| Title |
Force expression LNK suppresses interferon Gamma signaling |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
mRNA profiles of Control and LNK overexpressing cells were generated by deep sequencing using BGISEQ-500.
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| Contributor(s) |
Ding L, Sun Q, Edwards JJ, Fernández LT, Ran X, Zhou S, Scolyer RA, Wilmott JS, Thompson JF, Doan N, Said JW, Venkatachalam N, Xiao J, Loh X, Pein M, Xu L, Mullins DW, Yang H, Lin D, Koeffler HP |
| Citation(s) |
31110180 |
| Submission date |
Mar 04, 2019 |
| Last update date |
May 29, 2019 |
| Contact name |
SIQIN ZHOU |
| E-mail(s) |
siqin_5@hotmail.com
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| Organization name |
Cancer Science Institute of Singapore
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| Street address |
14 Medical Drive
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| City |
Singapore |
| ZIP/Postal code |
117599 |
| Country |
Singapore |
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| Platforms (1) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA525355 |
| SRA |
SRP187403 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE127764_RAW.tar |
398.2 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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