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LNK suppresses interferon signaling in melanoma.
Ding, Ling-Wen; Sun, Qiao-Yang; Edwards, Jarem J; Fernández, Lucia Torres; Ran, Xue-Bin; Zhou, Si-Qin; Scolyer, Richard A; Wilmott, James S; Thompson, John F; Doan, Ngan; Said, Jonathan W; Venkatachalam, Nachiyappan; Xiao, Jin-Fen; Loh, Xin-Yi; Pein, Maren; Xu, Liang; Mullins, David W; Yang, Henry; Lin, De-Chen; Koeffler, H Phillip.
Afiliação
  • Ding LW; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
  • Sun QY; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore. qiaoyangsun@gmail.com.
  • Edwards JJ; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Fernández LT; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Ran XB; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
  • Zhou SQ; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
  • Scolyer RA; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
  • Wilmott JS; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Thompson JF; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Doan N; Royal Prince Alfred Hospital, Sydney, Sydney, NSW, 2050, Australia.
  • Said JW; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Venkatachalam N; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Xiao JF; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Loh XY; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Pein M; Royal Prince Alfred Hospital, Sydney, Sydney, NSW, 2050, Australia.
  • Xu L; Santa Monica-University of California, Los Angeles Medical Center, Los Angeles, CA, 90095, USA.
  • Mullins DW; Santa Monica-University of California, Los Angeles Medical Center, Los Angeles, CA, 90095, USA.
  • Yang H; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
  • Lin DC; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
  • Koeffler HP; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Nat Commun ; 10(1): 2230, 2019 05 20.
Article em En | MEDLINE | ID: mdl-31110180
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Proteínas / Interferons / Peptídeos e Proteínas de Sinalização Intracelular / Melanoma Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Singapura
Texto completo
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Proteínas / Interferons / Peptídeos e Proteínas de Sinalização Intracelular / Melanoma Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Singapura