| Literature DB >> 22306001 |
Hla Win-Piazza1, Valentina E Schneeberger, Liwei Chen, Daniele Pernazza, Harshani R Lawrence, Said M Sebti, Nicholas J Lawrence, Jie Wu.
Abstract
Interferon-α2b (IFN-α2b) is used to treat melanoma but there is a need to improve its efficacy. IFN-α2b signaling requires STAT1/STAT2 tyrosine phosphorylation and is subject to negative regulation by phosphatases. In this study, we determined whether inhibition of the protein tyrosine phosphatase Shp2 could enhance IFN-α2b responses in human melanoma cells. Shp2 knockdown increased IFN-α2b-stimulated STAT1 Tyr-701 phosphorylation and ISRE-luciferase activity even though it did not affect STAT2 Tyr-690 phosphorylation in A375 cells. In A375 tumor xenografts, Shp2 knockdown enhanced the anti-melanoma effect of IFN-α2b. Furthermore, the Shp2 inhibitor SPI-112Me increased the IFN-α2b-induced STAT1 activation and anti-proliferative response in A375 and SK-MEL-2 cells. These results demonstrate that inhibition of Shp2 can enhance the anti-melanoma activity of IFN-α2b.Entities:
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Year: 2012 PMID： 22306001 PMCID： PMC3319810 DOI： 10.1016/j.canlet.2012.01.034
Source DB: PubMed Journal: Cancer Lett ISSN： 0304-3835 Impact factor: 8.679