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Title: LNK suppresses interferon signaling in melanoma
Authors: Ding, L.-W. 
Sun, Q.-Y. 
Edwards, J.J.
Fernández, L.T.
Ran, X.-B.
Zhou, S.-Q. 
Scolyer, R.A.
Wilmott, J.S.
Thompson, J.F.
Doan, N.
Said, J.W.
Venkatachalam, N.
Xiao, J.-F. 
Loh, X.-Y.
Pein, M.
Xu, L. 
Mullins, D.W.
Yang, H. 
Lin, D.-C.
Koeffler, H.P. 
Issue Date: 2019
Publisher: Nature Publishing Group
Citation: Ding, L.-W., Sun, Q.-Y., Edwards, J.J., Fernández, L.T., Ran, X.-B., Zhou, S.-Q., Scolyer, R.A., Wilmott, J.S., Thompson, J.F., Doan, N., Said, J.W., Venkatachalam, N., Xiao, J.-F., Loh, X.-Y., Pein, M., Xu, L., Mullins, D.W., Yang, H., Lin, D.-C., Koeffler, H.P. (2019). LNK suppresses interferon signaling in melanoma. Nature Communications 10 (1) : 2230. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: 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. © 2019, The Author(s).
Source Title: Nature Communications
ISSN: 20411723
DOI: 10.1038/s41467-019-09711-y
Rights: Attribution 4.0 International
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