SIPAR negatively regulates STAT3 signaling and inhibits progression of melanoma
2013; Elsevier BV; Volume: 25; Issue: 11 Linguagem: Inglês
10.1016/j.cellsig.2013.07.023
ISSN1873-3913
AutoresFangli Ren, Fuqin Su, Hongxiu Ning, Yangmeng Wang, Yongtao Geng, Yarui Feng, Yinyin Wang, Yanquan Zhang, Zhe Jin, Yi Li, Baoqing Jia, Zhijie Chang,
Tópico(s)interferon and immune responses
ResumoPersistently activated STAT3 is important for tumorigenesis in a variety of cancers, including melanoma. Although many co-factors in the regulation of STAT3 activity have been identified, it remains unclear how STAT3 phosphorylation is negatively regulated. Here, we report that SIPAR (STAT3-Interacting Protein As a Repressor) inhibits STAT3 activity by accelerating its dephosphorylation. We observed that SIPAR directly interacted with STAT3 upon IL-6 stimulation. Moreover, over-expression of SIPAR reduced, whereas depletion enhanced, the level of phosphorylated STAT3. We further demonstrated that SIPAR inhibited the growth of melanoma cells by decreasing the level of phosphorylated STAT3 and the expression of its target genes. These results suggest that SIPAR, functioning as a new negative regulator, inhibits STAT3 activity by enhancing its dephosphorylation and represses melanoma progression.
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