SIPAR negatively regulates STAT3 signaling and inhibits progression of melanoma

Fangli Ren; Fuqin Su; Hongxiu Ning; Yangmeng Wang; Yongtao Geng; Yarui Feng; Yinyin Wang; Yanquan Zhang; Zhe Jin; Yi Li; Baoqing Jia; Zhijie Chang

doi:10.1016/j.cellsig.2013.07.023

SIPAR negatively regulates STAT3 signaling and inhibits progression of melanoma

Cell Signal. 2013 Nov;25(11):2272-80. doi: 10.1016/j.cellsig.2013.07.023. Epub 2013 Jul 31.

Authors

Fangli Ren¹, Fuqin Su, Hongxiu Ning, Yangmeng Wang, Yongtao Geng, Yarui Feng, Yinyin Wang, Yanquan Zhang, Zhe Jin, Yi Li, Baoqing Jia, Zhijie Chang

Affiliation

¹ State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.

PMID: 23917203
DOI: 10.1016/j.cellsig.2013.07.023

Abstract

Persistently 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.

Keywords: Dephosphorylation; Melanoma; SIPAR; STAT3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / antagonists & inhibitors
Adaptor Proteins, Signal Transducing / genetics*
Adaptor Proteins, Signal Transducing / metabolism
Amino Acid Sequence
Animals
Cell Line, Tumor
Disease Progression
Gene Expression Regulation, Neoplastic*
Genes, Reporter
Humans
Interleukin-6 / pharmacology
Luciferases / genetics
Luciferases / metabolism
Male
Melanoma, Experimental / genetics*
Melanoma, Experimental / metabolism
Melanoma, Experimental / pathology
Mice
Mice, Nude
Molecular Sequence Data
NIH 3T3 Cells
Nuclear Proteins / antagonists & inhibitors
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Phosphorylation
STAT3 Transcription Factor / genetics*
STAT3 Transcription Factor / metabolism
Sequence Homology, Amino Acid
Signal Transduction / drug effects
Skin Neoplasms / genetics*
Skin Neoplasms / metabolism
Skin Neoplasms / pathology
Tumor Burden

Substances

Adaptor Proteins, Signal Transducing
Fam220a protein, mouse
Interleukin-6
Nuclear Proteins
STAT3 Transcription Factor
Stat3 protein, mouse
Luciferases